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1
Li, Lijin, Sharon M. Dial, Monika Schmelz, Margaret A. Rennels, and Neil M. Ampel. "Cellular Immune Suppressor Activity Resides in Lymphocyte Cell Clusters Adjacent to Granulomata in Human Coccidioidomycosis." Infection and Immunity 73, no. 7 (July 2005): 3923–28. http://dx.doi.org/10.1128/iai.73.7.3923-3928.2005.
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ABSTRACT The in situ immunologic response in human coccidioidomycosis remains undefined. To explore this further, pulmonary necrotizing coccidioidal granulomata were examined using immunohistochemical staining for lymphocyte subsets and for the cytokines interleukin-10 (IL-10) and gamma interferon (IFN-γ). Discrete perigranulomatous lymphocytic clusters were seen in eight of nine tissues examined. In these tissues, T lymphocytes (CD3+) significantly outnumbered B lymphocytes (CD20+) in the mantle area of the granulomata (P = 0.028), whereas the clusters were composed of roughly equal numbers of T and B lymphocytes. While the number of cells in the mantle expressing IL-10 was similar to those in the perigranulomatous clusters, there were significantly more cells expressing IFN-γ in the mantle than in the clusters (P = 0.037). Confocal microscopy revealed that CD4+ T lymphocytes and B lymphocytes are associated with IL-10 production. CD4+CD25+ T lymphocytes were identified in the perigranulomatous clusters but were not associated with IL-10 production. This is the first report noting perigranulomatous lymphocyte clusters and IL-10 in association with human coccidioidal granulomata and suggests that down-regulation of the cellular immune response is occurring within coccidioidal granulomata.
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Tait, Heidi. "Mechanisms behind the induction of Ttc7 transcription during B lymphocyte development(93.35)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 93.35. http://dx.doi.org/10.4049/jimmunol.184.supp.93.35.
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Abstract Changes in Ttc7 (tetratricopeptide repeat domain 7) transcription have been associated with changes in B lymphocyte signaling through changes in both the lymphopoietic environment and homeostasis of B lymphocyte development in mice with the Ttc7fsn/fsn(flaky skin) mutation. We have demonstrated that young Ttc7fsn/fsn mice exhibit decreased naive B lymphocyte populations in the bone marrow and spleen as compared to their wild type littermates, and that this disparity is exaggerated with age. The Ttc7fsn/fsn mutation also leads to excessive production of harmful B1b lymphocytes causing autoimmune disease closely related to SLE. This is significant as both autoimmune and aging human populations share similar B lymphocyte profiles. The evaluation of signaling events upstream of Ttc7 transcription will shed light on stage-specific B cell developmental signaling mechanisms in the bone marrow and spleen that cause immunological dysfunction. We have begun to classify B lymphocyte stages at which Ttc7 transcription rates fluctuate in pursuit of these signaling mechanisms. We have found Ttc7 to be transcribed in the bone marrow at early B lymphocyte stages and have evidence that its transcription is repressed at later stages in the spleen. To further support the hypothesis that induction of Ttc7 transcription during B cell development occurs in early B lymphocytes, we have also found that a 1kb segment of the promoter induces a higher rate of transcription in the pre-B 70Z/3 cell line.
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Lipsky, P. E., S. Hirohata, D. F. Jelinek, L. McAnally, and J. B. Splawski. "Regulation of Human B Lymphocyte Responsiveness." Scandinavian Journal of Rheumatology 17, sup76 (January 1988): 229–35. http://dx.doi.org/10.3109/03009748809102973.
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Uckun, F. M., D. A. Vallera, and S. L. Wee. "B lymphocyte regulation of human hematopoiesis." Journal of Immunology 135, no. 6 (December 1, 1985): 3817–22. http://dx.doi.org/10.4049/jimmunol.135.6.3817.
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Abstract Epstein Barr virus (EBV)-transformed B lymphoblastoid cell lines (BLCL) were derived from seven different individuals. The ability of BLCL supernatants to stimulate hematopoietic colony formation in vitro was tested in a conventional stem cell assay system. Supernatants promoted the growth of single (GM, E, MK) as well as multi-lineage (GEMM) colonies in bone marrow cultures. Our results indicate that EBV-transformed B lymphocytes produce cytokines that affect in vitro stem cell proliferation and differentiation. These studies demonstrate the regulatory potential of activated B lymphocytes in human hematopoiesis.
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Mun, Yeung-Chul, Kyoung-Eun Lee, Jung Mi Kwon, Seung-Hyun Nam, Eun Sun Yoo, Yun-Kyung Bae, Seung-Eun Lee, et al. "Establishment of Effective B Lymphocyte Ex Vivo Expansion on Human Cord Blood Using TPO, SCF, FL, IL-4, IL-10, and CD40L." Blood 104, no. 11 (November 16, 2004): 2882. http://dx.doi.org/10.1182/blood.v104.11.2882.2882.
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Abstract In respect to B lymphocyte-mediated immunity, characteristics of human cord blood are low counts of mature B lymphocytes, deficient expression of CD40L and cytokine production in CD4+ T lymphocytes, defect in the isotype switch of immunoglobulin and the activation of B lymphocytes, and low IgG production of B lymphocytes. These characteristics of the B lymphocyte from human cord blood lead to a delayed B lymphocyte-mediated immune reconstitution and an increased susceptibility to infections after a cord blood transplantation. The mechanism of immunological recostitution after cord blood transplantation has been examined from a variety of viewpoints in experimental models as well as clinical studies. However, problems of sustained immunodeficiency after cord blood transplantation remain to be resolved. The aim of the present study is to establish culture conditions that support the effective B lymphocyte expansion of human cord blood using IL-4, IL-10, and CD40L, to which cytokines are defected in B lymphocyte of human cord blood, and established conditions are compared to previously established cytokine combinations, TPO+SCF+FL in our Lab (Br J Haematol 107:176–185, 1999 & Stem Cells 21:228–235, 2003). To elucidate the effective B lymphocyte-mediated immune reconstitution of cord blood after ex vivo expansion, mononuclear cells, separated from density gradient of Ficoll system, and CD34+ purified cells, isolated from immunomicrobead(MiniMACS) system, were cultured with various combinations of cytokines (TPO+FL+SCF and/or IL-4, IL-10 and CD40L) for 2 weeks or 4 weeks. This then allowed for cytometric analysis after immunofluorescence stain with CD34, CD38 (for HSC analysis) and CD19, IgG and IgM (for B lymphocyte-mediated immune reconstitution) and CD4 (for T helper cell) and CD25 (for lymphocyte activation assay) to be performed. In the B lymphocyte expansion aspect, the immunoglobulin expression, and functional activity, expansion with the TPO+FL+SCF+IL-4+IL-10 combination showed best results in the expression of CD19, CD25, IgG, and IgM. However, the addition of CD40L to those culture condition did not increase expression of CD19, CD25, IgG, and IgM after the expansion of human cord blood. Expansion of CD34+ purified cells was superior to MNCs in the expression of CD19, CD25, IgG, and IgM. In consideration for the duration of cultures, the 2 week culture was superior to the 4 week culture with respect to graft stemness (CD34+CD38- fraction). Our data suggests most superior results were observed from the ex vivo expansion of CD34+ purified cells cultured for 2 weeks with TPO+FL+SCF+IL-4+IL-10, in the B lymphocyte-mediated immune reconstitution and graft stemness aspect. The results of this study warrant further investigation on effective B lymphocyte-mediated immune reconstitution after cord blood transplantation in vivo using ex vivo expanded cord blood.
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Dorward, D. "Interactions Between Mouse Lymphocytes And Borrelia Burgdorferi, The Infectious Agent Of Lyme Disease." Microscopy and Microanalysis 5, S2 (August 1999): 1242–43. http://dx.doi.org/10.1017/s143192760001953x.
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Lyme disease is a tick borne, multi-system disorder caused by low density systemic infections with the spirochete Borrelia burgdorferi. Without antimicrobial treatment, mammalian infections with these bacteria are persistent and chronic. Recent studies showed that B. burgdorferi can target, invade, and lyse both cultured and primary human B and T cells. Direct interactions between the spirochetes and lymphocytes also leads to adherence of B and T cell antigens on the surface of significant proportions of the bacteria . Adherent lymphocytic antigens inhibit binding of antibodies to prominent B. burgdorferi proteins, and interfere with classic complement-mediated killing, suggesting a possible role for spirochete-lymphocyte interactions in immune evasion.In order to develop an experimental animal model for assessing spirochete-lymphocyte interactions, B. burgdorferi and primary mouse lymphocytes were co-incubated and examined by electron microscopy. Mononuclear cells were separated from fresh mouse blood by Ficoll gradient centrifugation (ICN, Biomedicals, Aurora, Ohio).
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Matsushima, K., A. Procopio, H. Abe, G. Scala, J. R. Ortaldo, and J. J. Oppenheim. "Production of interleukin 1 activity by normal human peripheral blood B lymphocytes." Journal of Immunology 135, no. 2 (August 1, 1985): 1132–36. http://dx.doi.org/10.4049/jimmunol.135.2.1132.
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Abstract Interleukin 1 (IL 1) production by normal human B lymphocytes was investigated. Normal human peripheral blood B lymphocytes were purified by sequential separation with the use of Ficoll-Hypaque gradient centrifugation, sheep red blood cell rosette formation, Percoll gradients, and treatment with monoclonal antibodies (anti-Leu-M1, B73.1, and T101) and complement. Both purified large B lymphocytes (BL) and small B lymphocytes (BS) produced IL 1-like (thymocyte co-mitogenic and fibroblast mitogenic) activities in response to lipopolysaccharide. Maximal production of IL 1 activity by both BL and BS occurred at 48 hr. The m.w. of IL 1 activities from both BL and BS were about 20,000 with high pressure liquid chromatography, and the major isoelectric point of BL- and BS-derived IL 1 activity was 7.0. A rabbit anti-human monocyte IL 1 antiserum inhibited the activity of B cell-derived IL 1, suggesting antigenic similarities of monocyte- and B lymphocyte-derived IL 1 moieties. These data suggest that normal B lymphocyte-derived IL 1 activity is biochemically and immunologically similar to monocyte-derived IL 1.
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van Zelm, Menno C., Tomasz Szczepański, Mirjam van der Burg, and Jacques J. M. van Dongen. "Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion." Journal of Experimental Medicine 204, no. 3 (February 20, 2007): 645–55. http://dx.doi.org/10.1084/jem.20060964.
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The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro proliferation studies. We demonstrate that naive mature B lymphocytes, but not transitional B lymphocytes, undergo in vivo homeostatic proliferation in the absence of somatic mutations in the periphery. T cell–dependent B cell proliferation was substantially higher and showed higher frequencies of somatic hypermutation than T cell–independent responses, fitting with the robustness and high affinity of T cell–dependent antibody responses. More extensive proliferation and somatic hypermutation in antigen-experienced B lymphocytes from human adults compared to children indicated consecutive responses upon additional antigen exposures. Our combined observations unravel the contribution of proliferation to both B lymphocyte homeostasis and antigen-induced B cell expansion. We propose an important role for both processes in humoral immunity. These new insights will support the understanding of peripheral B cell regeneration after hematopoietic stem cell transplantation or B cell–directed antibody therapy, and the identification of defects in homeostatic or antigen-induced B cell proliferation in patients with common variable immunodeficiency or another antibody deficiency.
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Dohi, Keiichiro, William J. Kraemer, and Andrea M. Mastro. "Exercise increases prolactin-receptor expression on human lymphocytes." Journal of Applied Physiology 94, no. 2 (February 1, 2003): 518–24. http://dx.doi.org/10.1152/japplphysiol.00004.2002.
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Plasma prolactin has been shown to increase during stress; the immune system is responsive to prolactin and affected by stress. Therefore, this study was undertaken to investigate the effects of acute graded, maximal treadmill exercise on prolactin-receptor expression by lymphocytes. Eight healthy men underwent one exercise and one nonexercise session. Blood was sampled immediately before and after the exercise. On the day of the nonexercise session, two resting blood samples were obtained at the same times as the exercise session samples to act as baseline data. Plasma prolactin concentrations were significantly elevated in response to exercise and correlated positively with total prolactin-receptor expression per B lymphocyte. An increase in total prolactin-receptor expression per B lymphocyte in response to exercise also was observed. In addition, exercise significantly increased the total number of circulating B lymphocytes expressing prolactin receptor as well as the total number of circulating B lymphocytes. These data support the idea that exercise may enhance the interaction between immune target cells and prolactin, a stress hormone capable of enhancing immune function.
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Pals, S. T., G. Kraal, E. Horst, A. de Groot, R. J. Scheper, and C. J. Meijer. "Human lymphocyte-high endothelial venule interaction: organ-selective binding of T and B lymphocyte populations to high endothelium." Journal of Immunology 137, no. 3 (August 1, 1986): 760–63. http://dx.doi.org/10.4049/jimmunol.137.3.760.
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Abstract We wished to determine whether human lymphocytes, like their murine counterparts, show organ-specific interactions with high endothelial venules (HEV). Functional HEV-binding ability was measured by an in vitro assay of lymphocyte adherence to HEV in frozen sections of human lymphoid tissues which was adapted from rodent systems. It was found that human lymphocytes bind selectively to HEV and that, whereas mature T lymphocytes bind preferentially to HEV in peripheral lymph nodes and tonsils, B lymphocytes show preferential binding to HEV in GALT. Moreover, by analyzing the binding characteristics of T4+ and T8+ T cell populations, it was found that T8+ cells adhere preferentially to HEV in GALT and mesenteric lymph nodes and tonsil, and that T4+ cells bind slightly better to HEV in peripheral lymph nodes. The above findings indicate that organ--specific lymphocyte-endothelial cell recognition mechanisms exist also in humans, and suggest that these mechanisms play an important role in normal and pathologic lymphocyte traffic.
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Sung, S. S., L. K. Jung, J. A. Walters, E. W. Jeffes, G. A. Granger, and S. M. Fu. "Production of lymphotoxin by isolated human tonsillar B lymphocytes and B lymphocyte cell lines." Journal of Clinical Investigation 84, no. 1 (July 1, 1989): 236–43. http://dx.doi.org/10.1172/jci114146.
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Gu, B. J., W. Y. Zhang, L. J. Bendall, I. P. Chessell, G. N. Buell, and J. S. Wiley. "Expression of P2X7purinoceptors on human lymphocytes and monocytes: evidence for nonfunctional P2X7receptors." American Journal of Physiology-Cell Physiology 279, no. 4 (October 1, 2000): C1189—C1197. http://dx.doi.org/10.1152/ajpcell.2000.279.4.c1189.
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Lymphocytes from normal subjects and patients with B-chronic lymphocytic leukemia (B-CLL) show functional responses to extracellular ATP characteristic of the P2X7receptor (previously termed P2Z). These responses include opening of a cation-selective channel/pore that allows entry of the fluorescent dye ethidium and activation of a membrane metalloprotease that sheds the adhesion molecule L-selectin. The surface expression of P2X7receptors was measured in normal leucocytes, platelets, and B-CLL lymphocytes and correlated with their functional responses. Monocytes showed four- to fivefold greater expression of P2X7than B, T, and NK lymphocytes, whereas P2X7expression on neutrophils and platelets was weak. All cell types demonstrated abundant intracellular expression of this receptor. All 12 subjects with B-CLL expressed lymphocyte P2X7at about the same level as B lymphocytes from normal subjects. P2X7function, measured by ATP-induced uptake of ethidium, correlated closely with surface expression of this receptor in normal and B-CLL lymphocytes and monocytes ( n = 47, r = 0.70; P< 0.0001). However, in three patients the ATP-induced uptake of ethidium into the malignant B lymphocytes was low or absent. The lack of P2X7function in these B lymphocytes was confirmed by the failure of ATP to induce Ba2+uptake into their lymphocytes. This lack of function of the P2X7receptor resulted in a failure of ATP-induced shedding of L-selectin, an adhesion molecule that directs the recirculation of lymphocytes from blood into the lymph node.
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Torres, R. M., and E. A. Clark. "Differential increase of an alternatively polyadenylated mRNA species of murine CD40 upon B lymphocyte activation." Journal of Immunology 148, no. 2 (January 15, 1992): 620–26. http://dx.doi.org/10.4049/jimmunol.148.2.620.
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Abstract CD40 is an integral membrane glycoprotein found on the surface of human B lymphocytes. Antibodies specific for CD40 have been shown to augment proliferation of activated B lymphocytes, prevent B lymphocyte apoptosis, and prolong the maintenance of normal B lymphocytes in culture. As a step toward developing an in vivo system to examine CD40 function, a molecular clone encoding the murine homologue of the human CD40 B lymphocyte surface Ag was isolated and characterized. Throughout their open reading frames, the murine and human proteins shared 62% predicted amino acid identity. Within the cytoplasmic domain, which includes a completely conserved region known to be important for signaling by human CD40, the CD40 homologues are 78% identical. The human and murine proteins are members of a new cytokine receptor family, which includes the receptors for nerve growth factor and TNF-alpha, that are homologous in their cysteine-rich extracellular domains. The murine CD40 gene is expressed in B lymphocytes as two mRNA species generated by alternative usage of polyadenylation signals in the 3' untranslated region. The activation of B lymphocytes differentially increases the relative levels of these two mRNA transcripts suggesting a posttranscriptional mechanism for the regulation of CD40 surface expression.
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Fazel, S. B., S. E. Howie, A. S. Krajewski, and D. Lamb. "B lymphocyte accumulations in human pulmonary sarcoidosis." Thorax 47, no. 11 (November 1, 1992): 964–67. http://dx.doi.org/10.1136/thx.47.11.964.
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Yanaba, Koichi, Jean-David Bouaziz, Takashi Matsushita, Cynthia M. Magro, E. William St.Clair, and Thomas F. Tedder. "B-lymphocyte contributions to human autoimmune disease." Immunological Reviews 223, no. 1 (June 2008): 284–99. http://dx.doi.org/10.1111/j.1600-065x.2008.00646.x.
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de los Toyos, J., S. Jalkanen, and EC Butcher. "Flow cytometric analysis of the Hermes homing-associated antigen on human lymphocyte subsets." Blood 74, no. 2 (August 1, 1989): 751–60. http://dx.doi.org/10.1182/blood.v74.2.751.751.
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Abstract The homing of lymphocytes is controlled by interactions with high endothelial venules (HEV), specialized vessels that define sites of lymphocyte extravasation into lymph nodes and inflamed tissues. In humans, lymphocyte-HEV binding involves a lymphocyte surface glycoprotein (GP) of 85 to 95 kd (CD44, H-CAM), defined by monoclonal antibody (MoAb) Hermes-1. To define the expression of this homing- associated adhesion molecule during human lymphocyte development, we performed two-color immunofluorescence analyses of human bone marrow (BM), thymus, peripheral blood (PB), and tonsillar lymphocytes. The highest levels of Hermes-1 antigen are displayed by circulating B and T cells in the blood, which are uniformly positive and bear roughly twice the level of antigen present on mature lymphocytes within organized lymphoid tissues and BM. “Immature” (CD4+, CD8+) T cells in the thymus are Hermes-1lo to-, whereas thymocytes of mature phenotype (CD4+ or CD8+) are positive. The Hermes-1 antigen is present at high levels on the same population of thymocytes that bears high surface levels of CD3, a component of the T-cell antigen receptor complex, suggesting that levels of T-cell homing and antigen receptors characteristic of mature peripheral T cells appear coordinately during thymocyte maturation/selection. Essentially all T cells in the periphery are Hermes-1hi, including T blasts, and the homing-associated antigen is maintained at high levels on T cells stimulated in vitro by phytohemagglutinin (PHA) and on interleukin-2 (IL-2) maintained T-cell clones and lines. In contrast, although most resting IgD+ B cells are positive a significant fraction of B cells in tonsils are Hermes-1lo to- ; these cells are predominantly PNAhi, IgD-, and CD20hi, a phenotype characteristic of sessile, activated B cells in germinal centers. In all lymphocyte populations examined, there is a linear correlation in staining for Hermes-1 and for Hermes-3, an antibody that defines a distinct functionally important epitope on this molecule. The results demonstrate a precise regulation of this homing-associated antigen during lymphocyte differentiation.
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de los Toyos, J., S. Jalkanen, and EC Butcher. "Flow cytometric analysis of the Hermes homing-associated antigen on human lymphocyte subsets." Blood 74, no. 2 (August 1, 1989): 751–60. http://dx.doi.org/10.1182/blood.v74.2.751.bloodjournal742751.
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The homing of lymphocytes is controlled by interactions with high endothelial venules (HEV), specialized vessels that define sites of lymphocyte extravasation into lymph nodes and inflamed tissues. In humans, lymphocyte-HEV binding involves a lymphocyte surface glycoprotein (GP) of 85 to 95 kd (CD44, H-CAM), defined by monoclonal antibody (MoAb) Hermes-1. To define the expression of this homing- associated adhesion molecule during human lymphocyte development, we performed two-color immunofluorescence analyses of human bone marrow (BM), thymus, peripheral blood (PB), and tonsillar lymphocytes. The highest levels of Hermes-1 antigen are displayed by circulating B and T cells in the blood, which are uniformly positive and bear roughly twice the level of antigen present on mature lymphocytes within organized lymphoid tissues and BM. “Immature” (CD4+, CD8+) T cells in the thymus are Hermes-1lo to-, whereas thymocytes of mature phenotype (CD4+ or CD8+) are positive. The Hermes-1 antigen is present at high levels on the same population of thymocytes that bears high surface levels of CD3, a component of the T-cell antigen receptor complex, suggesting that levels of T-cell homing and antigen receptors characteristic of mature peripheral T cells appear coordinately during thymocyte maturation/selection. Essentially all T cells in the periphery are Hermes-1hi, including T blasts, and the homing-associated antigen is maintained at high levels on T cells stimulated in vitro by phytohemagglutinin (PHA) and on interleukin-2 (IL-2) maintained T-cell clones and lines. In contrast, although most resting IgD+ B cells are positive a significant fraction of B cells in tonsils are Hermes-1lo to- ; these cells are predominantly PNAhi, IgD-, and CD20hi, a phenotype characteristic of sessile, activated B cells in germinal centers. In all lymphocyte populations examined, there is a linear correlation in staining for Hermes-1 and for Hermes-3, an antibody that defines a distinct functionally important epitope on this molecule. The results demonstrate a precise regulation of this homing-associated antigen during lymphocyte differentiation.
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Trueblood, Esther S., Wendy C. Brown, Guy H. Palmer, William C. Davis, Diana M. Stone, and Terry F. McElwain. "B-Lymphocyte Proliferation during Bovine Leukemia VirusInduced Persistent Lymphocytosis Is Enhanced by T-Lymphocyte-Derived Interleukin-2." Journal of Virology 72, no. 4 (April 1, 1998): 3169–77. http://dx.doi.org/10.1128/jvi.72.4.3169-3177.1998.
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ABSTRACT Bovine leukemia virus (BLV)-induced persistent lymphocytosis is characterized by a polyclonal expansion of CD5+ B lymphocytes. To examine the role of the cytokine microenvironment in this virus-induced B-lymphocyte expansion, the expression of interleukin-2 (IL-2), IL-4, IL-10, and gamma interferon (IFN-γ) mRNA, was measured in stimulated peripheral blood mononuclear cells from persistently lymphocytotic BLV-infected cows, nonlymphocytotic BLV-infected cows, and uninfected cows. IL-2 and IL-10 mRNA expression and IL-2 functional activity were significantly increased when peripheral blood mononuclear cells from persistently lymphocytotic cows were stimulated with concanavalin A (ConA). Additionally, during persistent lymphocytosis, peak IL-2 and IL-10 mRNA expression was delayed, and elevated expression was prolonged. To determine the potential biologic importance of increased IL-2 and IL-10 expression, the response of isolated B lymphocytes from persistently lymphocytotic cows to human recombinant cytokines and to cytokine-containing supernatants from isolated T lymphocytes was examined. While recombinant human IL-10 (rhIL-10) did not consistently induce detectable changes, rhIL-2 increased viral protein (p24) and IL-2 receptor expression in isolated B lymphocytes from persistently lymphocytotic cows. Additionally, rhIL-2 and supernatant from ConA-stimulated T lymphocytes enhanced B-lymphocyte proliferation. The stimulatory activity of the T-lymphocyte supernatant could be completely inhibited with a polyclonal anti-rhIL-2 antibody. Finally, polyclonal anti-rhIL-2 antibody, as well as anti-BLV antibody, inhibited spontaneous proliferation of peripheral blood mononuclear cells from persistently lymphocytotic cows, demonstrating that the spontaneous lymphoproliferation characteristic of BLV-induced persistent lymphocytosis is IL-2 dependent and antigen dependent. Collectively, these findings strongly suggest that increased T-lymphocyte expression of IL-2 in BLV-infected cows contributes to development and/or maintenance of persistent B lymphocytosis.
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Machado, Heather E., Nina Friesgaard Øbro, Emily Mitchell, Megan Davies, Anthony R. Green, Kourosh Saeb-Parsy, Daniel James Hodson, David Kent, and Peter J. Campbell. "Life History of Normal Human Lymphocytes Revealed By Somatic Mutations." Blood 134, Supplement_1 (November 13, 2019): 1045. http://dx.doi.org/10.1182/blood-2019-128188.
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Introduction: Mature blood cells harbor a mixture of mutations inherited from ancestral hematopoietic stem cells (HSCs) and mutations accumulated after maturation. The landscape of these somatic mutations in normal blood is poorly mapped, with questions as simple as "how many mutations does a memory T cell accumulate throughout life?" remaining unanswered. This gap in our knowledge is particularly relevant for hematopoietic malignancy- while we know that lymphomas derive from lymphocytes of particular stages of differentiation, we do not know if the patterns we see are reflected in their normal counterparts. Results: In order to characterize normal somatic mutation in lymphocytes, we performed single-cell expansion and whole genome sequencing of over 600 T and B lymphocytes and 200 HSC and progenitor cells across 5 individuals (ages 0-85). All lymphocyte subsets show increased mutation burden with respect to HSCs across all classes of variants (Figure 1). Some of this increase can explained by lymphocyte-specific mutational processes, such as the activity of RAG, accounting for at least 20% of observed structural variants. We also find a striking variation in mutation burden within and between lymphocyte subsets. Microenvironment specific mutational processes dominate the observed differences. Examples of this include germinal center ("non-canonical AID") mutations in memory B cells and UV-like mutations in memory T cells (putatively skin resident cells). Naive B and T cells show a lack of variation in discrete mutational patterns relative to their memory counterparts, and have mutational profiles and mutation burdens more similar to that of HSCs. We also observe differences in the mutational patterns between B and T cells that are indicative of the increased divergence of T lymphocytes from the HSC pool. In general, the mutation burden we observe in normal lymphocytes approach those seen in lymphoma. Conclusions: Our work highlights the substantial genetic diversity in normal lymphocytes, with some cells accumulating thousands of mutations on top of those inherited from the HSC compartment. These mutations can be used to describe the life history of each individual lymphocyte including their exposure to specific microenvironments. Our findings shed light on the biology of these cells and will help differentiate between normal and disease processes. Figure 1 Disclosures No relevant conflicts of interest to declare.
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Cavender, D. E., D. O. Haskard, B. Joseph, and M. Ziff. "Interleukin 1 increases the binding of human B and T lymphocytes to endothelial cell monolayers." Journal of Immunology 136, no. 1 (January 1, 1986): 203–7. http://dx.doi.org/10.4049/jimmunol.136.1.203.
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Abstract Lymphocyte binding to specialized high-endothelial venules (HEV) in lymph nodes and Peyer's patches is the first step in normal lymphocyte emigration and recirculation. The development and maintenance of HEV in these lymphoid organs are thought to be immunologically controlled. Because postcapillary venules in chronic inflammatory tissue often resemble the HEV of lymphoid tissue and may also be a site of lymphocyte emigration, examination of the effects of immunologic and inflammatory mediators on endothelial cells (EC) may provide important information about the physiology of both normal lymphocyte recirculation and chronic inflammation. It is reported here that treatment of human umbilical vein EC monolayers in vitro with affinity-purified human interleukin 1 (IL 1) markedly enhances the binding of both B and T lymphocytes. Increased binding was observed within 1 h of treatment of EC with as little as 0.04 U/ml IL 1. This effect of IL 1 was EC-specific, because pretreatment of T cells or human skin fibroblasts with IL 1 did not increase the binding of lymphocytes. Stimulation of binding required active EC metabolism because incubation of EC with IL 1 at 4 degrees C, or prior fixation of EC, prevented enhanced binding. The action of IL 1 was not associated with EC damage. The secretion of IL 1 by macrophages and perhaps other cells in inflammatory lesions may exert a positive feedback signal on EC to enhance further emigration of lymphocytes into the inflammatory focus.
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Berry, Kacey, Daniela S. Farias-Itao, Lea T. Grinberg, Edward D. Plowey, Julie A. Schneider, Roberta D. Rodriguez, Claudia K. Suemoto, and Marion S. Buckwalter. "B and T Lymphocyte Densities Remain Stable With Age in Human Cortex." ASN Neuro 13 (January 2021): 175909142110181. http://dx.doi.org/10.1177/17590914211018117.
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One hallmark of human aging is increased brain inflammation represented by glial activation. With age, there is also diminished function of the adaptive immune system, and modest decreases in circulating B- and T-lymphocytes. Lymphocytes traffic through the human brain and reside there in small numbers, but it is unknown how this changes with age. Thus we investigated whether B- and T-lymphocyte numbers change with age in the normal human brain. We examined 16 human subjects in a pilot study and then 40 human subjects from a single brain bank, ranging in age from 44–96 years old, using rigorous criteria for defining neuropathological changes due to age alone. We immunostained post-mortem cortical tissue for B- and T-lymphocytes using antibodies to CD20 and CD3, respectively. We quantified cell density and made a qualitative assessment of cell location in cortical brain sections, and reviewed prior studies. We report that density and location of both B- and T-lymphocytes do not change with age in the normal human cortex. Solitary B-lymphocytes were found equally in intravascular, perivascular, and parenchymal locations, while T-lymphocytes appeared primarily in perivascular clusters. Thus, any change in number or location of lymphocytes in an aging brain may indicate disease rather than normal aging.
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Link, DC, and M. Zutter. "The proto-oncogene c-fgr is expressed in normal mantle zone B lymphocytes and is developmentally regulated during myelomonocytic differentiation in vivo." Blood 85, no. 2 (January 15, 1995): 472–79. http://dx.doi.org/10.1182/blood.v85.2.472.472.
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Abstract The proto-oncogene c-fgr is a member of the c-src gene family of cytoplasmic tyrosine kinases. Previous studies have suggested that it is normally expressed in neutrophils, monocytes, macrophages, and natural killer cells. c-fgr is also expressed in the B cells of certain lymphoproliferative disorders, namely, Epstein-Barr virus-associated lymphoproliferative disease, and in chronic lymphocytic leukemia, but it has not previously been detected in normal or reactive human lymphoid tissue. In this study we have determined the pattern of p55c- fgr protein expression in normal human hematopoietic and lymphoid tissues at the single-cell level using immunohistochemical and immunofluorescent techniques. We show that p55c-fgr expression is developmentally regulated with high-level expression first evident at the myelocyte stage of myeloid differentiation. In addition, we show that p55c-fgr is expressed in circulating B lymphocytes isolated from chronic lymphocytic leukemia patients but is not expressed in normal circulating B lymphocytes. Surprisingly, p55c-fgr is also expressed in a subpopulation of normal B lymphocytes, the mantle zone B lymphocytes. This demonstration that p55c-fgr is expressed in a normal B-lymphocyte subpopulation suggests that its expression in certain B-cell lymphoproliferative disorders may be an indirect consequence of, rather than a primary cause of, the neoplastic transformation process.
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Link, DC, and M. Zutter. "The proto-oncogene c-fgr is expressed in normal mantle zone B lymphocytes and is developmentally regulated during myelomonocytic differentiation in vivo." Blood 85, no. 2 (January 15, 1995): 472–79. http://dx.doi.org/10.1182/blood.v85.2.472.bloodjournal852472.
Full textAbstract:
The proto-oncogene c-fgr is a member of the c-src gene family of cytoplasmic tyrosine kinases. Previous studies have suggested that it is normally expressed in neutrophils, monocytes, macrophages, and natural killer cells. c-fgr is also expressed in the B cells of certain lymphoproliferative disorders, namely, Epstein-Barr virus-associated lymphoproliferative disease, and in chronic lymphocytic leukemia, but it has not previously been detected in normal or reactive human lymphoid tissue. In this study we have determined the pattern of p55c- fgr protein expression in normal human hematopoietic and lymphoid tissues at the single-cell level using immunohistochemical and immunofluorescent techniques. We show that p55c-fgr expression is developmentally regulated with high-level expression first evident at the myelocyte stage of myeloid differentiation. In addition, we show that p55c-fgr is expressed in circulating B lymphocytes isolated from chronic lymphocytic leukemia patients but is not expressed in normal circulating B lymphocytes. Surprisingly, p55c-fgr is also expressed in a subpopulation of normal B lymphocytes, the mantle zone B lymphocytes. This demonstration that p55c-fgr is expressed in a normal B-lymphocyte subpopulation suggests that its expression in certain B-cell lymphoproliferative disorders may be an indirect consequence of, rather than a primary cause of, the neoplastic transformation process.
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Vera, Juan, Barbara Savoldo, Stephane Vigouroux, Ettore Biagi, Martin Pule, Claudia Rossig, Jessie Wu, et al. "T lymphocytes redirected against the κ light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells." Blood 108, no. 12 (December 1, 2006): 3890–97. http://dx.doi.org/10.1182/blood-2006-04-017061.
Full textAbstract:
AbstractThere has been interest in generating T cells expressing chimeric artificial receptors (CARs) targeting CD19/CD20 antigens to treat B-cell lymphomas. If successful, however, this approach would likely impair humoral immunity because T cells may persist long-term. Most low-grade lymphoma and chronic lymphocytic leukemia (B-CLL) cells express monoclonal immunoglobulins carrying either κ or λ light chains. We, therefore, explored whether T lymphocytes could be genetically modified to target the tumor-associated light chain, sparing B lymphocytes expressing the reciprocal light chain, and consequently reduce impairment of humoral immunity. We found that T lymphocytes expressing the anti-κ light chain CAR showed cytotoxic activity against Igκ+ tumor cell lines and B-CLL cells both in vitro and in vivo. We also found that the incorporation of the CD28 endodomain within the CAR enhanced the in vitro and in vivo expansion of transgenic T cells after tumor-associated antigen stimulation. Free Igκ+ did not compromise the ability of redirected T lymphocytes to eliminate Igκ+ tumors because these free immunoglobulins served to sustain proliferation of CAR-CD28 transgenic T cells. Thus, adoptive transfer of T lymphocytes targeting the appropriate light chain could be a useful immunotherapy approach to treat B-lymphocyte malignancies that clonally express immunoglobulin without entirely compromising humoral immunity.
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Ambrus, J. L., M. G. Peters, A. S. Fauci, and E. J. Brown. "The Ba fragment of complement factor B inhibits human B lymphocyte proliferation." Journal of Immunology 144, no. 5 (March 1, 1990): 1549–53. http://dx.doi.org/10.4049/jimmunol.144.5.1549.
Full textAbstract:
Abstract Normal human B lymphocyte function is finely regulated by both positive and negative signals at each stage of activation, proliferation, and differentiation. Activation signals include antigen and surface Ig cross-linking agents such as anti-mu or anti-delta. Signals inducing proliferation include IL-2, high m.w.-B cell growth factor (BCGF), and low m.w.-BCGF. IL-2 as well as IL-6 and other partially characterized B cell differentiation factors can induce terminal differentiation of proliferating B cells into Ig-secreting plasma cells. Various C components have been described to regulate B cell function including Bb that enhances proliferation, C5a that enhances Ig production, and C3a that inhibits Ig production. In our study, we examined the ability of the factor B cleavage fragment Ba to influence human B cell function. Ba did not affect the activation of resting B cells but inhibited the proliferation of activated B cells stimulated with either high m.w.-BCGF or low m.w.-BCGF. The inhibition occurred with doses of Ba as low as 1 microgram/ml (29 nM). Ba was found to bind to activated human B lymphocytes in a saturable manner with an apparent K of approximately 25 nM and an apparent Bmax of 56,000 sites/cell. A peptide made of the carboxy terminal 10 amino acids of Ba (GHGPGEQQKR), was also found to inhibit growth factor induced proliferation of activated B cells but at an ID50 of approximately 5 microM. Finally, Ba was found to inhibit the terminal differentiation of Staphylococcus aweus Cowan-activated B cells stimulated with B cell differentiation factors but not Ig secretion by the partially differentiated EBV-transformed cell line SKW.6. Thus, concentrations of Ba achievable in vivo at sites of active inflammation were found to act on human B lymphocytes by inhibiting their proliferation. This may act to limit the immune response to a specific antigenic challenge.
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Charpentier, Eléna, Catherine Marques, Sandie Ménard, Pamela Chauvin, Emilie Guemas, Claire Cottrel, Sophie Cassaing, et al. "New Insights into Blood Circulating Lymphocytes in Human Pneumocystis Pneumonia." Journal of Fungi 7, no. 8 (August 11, 2021): 652. http://dx.doi.org/10.3390/jof7080652.
Full textAbstract:
The host lymphocyte response is decisive in Pneumocystis pneumonia (PCP) pathophysiology but little is known of the specific roles of lymphocyte subpopulations in this fungal infection. Peripheral NK, NKT, B, TCD4+ and TCD8+ subpopulations were compared by immunophenotyping between 20 patients diagnosed with PCP (PCP(+)] and 20 uninfected immunosuppressed patients (PCP(−)). Among PCP(+) subjects, the lymphocyte populations were also compared between surviving and deceased patients. Low B cell count (<40 cells/µL) was more frequent in PCP(+) than in PCP(−) patients (p = 0.03), while there was no difference for the TCD4 count. Among the PCP(+) group, the 7 deceased patients had lower Th1 (p = 0.02) and Tc1 (p = 0.03) populations, higher Th2 response (p = 0.03), higher effector TCD8 (p < 0.01), lower central memory TCD8 (p = 0.04) and reduced NK cells (p = 0.02) compared with the 13 survivors. Th1/Th2 ratio < 17, CD8 Tc1 < 44%, effector TCD8 < 25%, central memory TCD8 < 4%, NK cells < 50 cells/µL and total lymphocytes < 0.75 G/L were associated with a higher risk of mortality (p = 0.003, p = 0.007, p = 0.0007, p = 0.004, p = 0.02 and p = 0.019, respectively). The traditional analysis of TCD4 and TCD8 populations may be insufficient in the context of PCP. It could be completed by using B cells to predict the risk of PCP, and by using lymphocyte subpopulations or total lymphocyte count, which are easy to obtain in all health care facilities, to evaluate PCP prognosis.
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Itoua Maïga, Rayelle, Guillaume Bonnaure, Josiane Tremblay Rochette, and Sonia Néron. "Human CD38hiCD138+Plasma Cells Can Be Generated In Vitro from CD40-Activated Switched-Memory B Lymphocytes." Journal of Immunology Research 2014 (2014): 1–14. http://dx.doi.org/10.1155/2014/635108.
Full textAbstract:
B lymphocyte differentiation into long-lived plasma cells is the keystone event for the production of long-term protective antibodies. CD40-CD154 and CD27-CD70 interactions are involved in human B lymphocyte differentiation into CD38hiCD138+cells in vivo as well as in vitro. In this study, we have compared these interactions in their capacity to drive switched-memory B lymphocytes differentiation into CD38hiCD138+plasma cells. The targeted B lymphocytes were isolated from human peripheral blood, expanded for 19 days, and then submitted to CD70 or CD154 interactions for 14 days. The expanded B lymphocytes were constitutively expressing CD39, whereas CD31’s expression was noticed only following the in vitro differentiation step (day 5) and was exclusively present on the CD38hicell population. Furthermore, the generated CD38hiCD138+cells showed a higher proportion of CD31+cells than the CD38hiCD138-cells. Besides, analyses done with human blood and bone marrow plasma cells showed that in vivo and de novo generated CD38hiCD138+cells have a similar CD31 expression profile but are distinct according to their reduced CD39 expression level. Overall, we have evidences that in vitro generated plasma cells are heterogeneous and appear as CD39+precursors to the ones present in bone marrow niches.
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Thurlow, P. J., L. Kerrigan, R. A. Harris, and I. F. McKenzie. "Analysis of human bone marrow with monoclonal antibodies." Journal of Histochemistry & Cytochemistry 33, no. 12 (December 1985): 1183–89. http://dx.doi.org/10.1177/33.12.2415573.
Full textAbstract:
In order to study the antigenic phenotype of different hemopoietic cells, we used a series of monoclonal antibodies to investigate normal bone marrow in a standard immunofluorescence assay. The antibodies detected the following antigens: HLA-ABC, beta 2-microglobulin (beta 2m), HLA-DR (Ia), a lymphocyte subset and specific antigen (T and B) HuLy-m2, m3, T lymphocyte antigen (HuLy-m1), lymphocyte T200 antigen (HuLy-m4), a viral-associated antigen (HuLy-m5), and platelet-specific glycoproteins IIb-IIIa (HuPl-m1). The following results were obtained: (a) normoblasts were weakly HLA-ABC+, beta 2m+ and Ia-; all other lymphocyte and platelet antigens were not detected. (b) Myeloid cells at all stages of differentiation (promyelocytes, myelocytes, metamyelocytes, and neutrophils) were HLA-ABC+; beta 2m+; HuLy-m1-, m2-, m3+/- (20%), m4+, m5+/- (20%); HuPl-m1-; in addition, promyelocytes and myelocytes were Ia+ but neutrophils and metamyelocytes were Ia-. (c) Lymphocytes were HLA-ABC+, beta 2m+, Ia+/- (20-30%), HuLy-m1+/- (40-50%), m2+/- (60-70%), m3+, m4+, m5+; Pl-m1-. (d) Platelets and megakaryocytes were HLA-ABC+; beta 2m+; Ia-; HuLy-m1+-, m2-, m3-, m4-, m5-, HuPl-m1+, and the putative "megakaryocyte precursors" were HuPl-m1+, Ia-, HuLy-m1-. The different cell types in bone marrow could readily be distinguished, particularly cells of the myeloid series (Ia and HuLy-m4, m5), lymphocytes (Ia and HuLy-m1, m2, m3), and platelets and their precursor cells (HuPl-m1). This simple method of defining cellular phenotypes in bone marrow has demonstrated the practicality of using monoclonal antibodies to identify marrow cells and should be of diagnostic value.
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Feldman, L., and N. Dainiak. "B-lymphocyte-derived erythroid burst-promoting activity is distinct from other known lymphokines." Blood 73, no. 7 (May 15, 1989): 1814–20. http://dx.doi.org/10.1182/blood.v73.7.1814.1814.
Full textAbstract:
Abstract Previously we have demonstrated that, in contrast to various panspecific or multilineage hematopoietic growth factors, lymphocyte- derived erythroid burst-promoting activity (BPA) is lineage specific, stimulating BFU-E proliferation in serum-free culture by up to 600% of control values while failing to enhance nonerythroid colony formation. To further determine the cellular source(s) of this important erythropoietic growth regulator, we have separated normal nonadherent peripheral blood and splenic lymphocytes by nylon wool fractionation, SRBC rosetting, and panning with monoclonal antibodies (MoAbs). These unstimulated T- and B-lymphocyte-enriched populations were used as cell sources to produce conditioned media (CM) and to prepare plasma membranes (PM). When CM fractions or purified PM were assayed in serum- free human bone marrow culture, BPA was localized entirely to the B- lymphocyte-derived fractions. While CM or PM from unstimulated T lymphocytes failed to stimulate BFU-E proliferation, activation of T cells by either phytohemagglutinin-M (1%) or concanavalin A (Con A; 5 micrograms/mL) induced the expression of a factor on the PM and in the resultant CM that stimulated the formation of erythroid bursts. In addition to enhancing BFU-E proliferation, this T-cell factor stimulated the proliferation of CFU-GM and CFU-GEMM in serum-free culture. When compared biochemically (in terms of temperature stability, localization by ammonium sulfate fractionation, and sensitivity to dithiothreitol) or immunochemically (using antibodies specific for lymphocyte-derived BPA, GM-CSF, or interleukin-3 [IL-3]), as well as by lineage specificity, B- and activated T-lymphocyte- derived growth factors appeared to be distinct. The burst stimulatory activities expressed by recombinant human GM-CSF and IL-3 were immunologically distinct from that associated with octylglucoside extracts of plasma membranes from resting B lymphocytes. Our results suggest that the BFU-E-directed growth-promoting activity released from activated T lymphocytes is apparently due to GM-CSF, while both resting and mitogen-stimulated normal B lymphocytes express erythroid-specific BPA and neither GM-CSF nor IL-3.
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Feldman, L., and N. Dainiak. "B-lymphocyte-derived erythroid burst-promoting activity is distinct from other known lymphokines." Blood 73, no. 7 (May 15, 1989): 1814–20. http://dx.doi.org/10.1182/blood.v73.7.1814.bloodjournal7371814.
Full textAbstract:
Previously we have demonstrated that, in contrast to various panspecific or multilineage hematopoietic growth factors, lymphocyte- derived erythroid burst-promoting activity (BPA) is lineage specific, stimulating BFU-E proliferation in serum-free culture by up to 600% of control values while failing to enhance nonerythroid colony formation. To further determine the cellular source(s) of this important erythropoietic growth regulator, we have separated normal nonadherent peripheral blood and splenic lymphocytes by nylon wool fractionation, SRBC rosetting, and panning with monoclonal antibodies (MoAbs). These unstimulated T- and B-lymphocyte-enriched populations were used as cell sources to produce conditioned media (CM) and to prepare plasma membranes (PM). When CM fractions or purified PM were assayed in serum- free human bone marrow culture, BPA was localized entirely to the B- lymphocyte-derived fractions. While CM or PM from unstimulated T lymphocytes failed to stimulate BFU-E proliferation, activation of T cells by either phytohemagglutinin-M (1%) or concanavalin A (Con A; 5 micrograms/mL) induced the expression of a factor on the PM and in the resultant CM that stimulated the formation of erythroid bursts. In addition to enhancing BFU-E proliferation, this T-cell factor stimulated the proliferation of CFU-GM and CFU-GEMM in serum-free culture. When compared biochemically (in terms of temperature stability, localization by ammonium sulfate fractionation, and sensitivity to dithiothreitol) or immunochemically (using antibodies specific for lymphocyte-derived BPA, GM-CSF, or interleukin-3 [IL-3]), as well as by lineage specificity, B- and activated T-lymphocyte- derived growth factors appeared to be distinct. The burst stimulatory activities expressed by recombinant human GM-CSF and IL-3 were immunologically distinct from that associated with octylglucoside extracts of plasma membranes from resting B lymphocytes. Our results suggest that the BFU-E-directed growth-promoting activity released from activated T lymphocytes is apparently due to GM-CSF, while both resting and mitogen-stimulated normal B lymphocytes express erythroid-specific BPA and neither GM-CSF nor IL-3.
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Freedman, AS, JM Munro, K. Rhynhart, P. Schow, J. Daley, N. Lee, J. Svahn, L. Eliseo, and LM Nadler. "Follicular dendritic cells inhibit human B-lymphocyte proliferation." Blood 80, no. 5 (September 1, 1992): 1284–88. http://dx.doi.org/10.1182/blood.v80.5.1284.1284.
Full textAbstract:
Abstract In germinal centers, B lymphocytes are intimately associated with follicular dendritic cells (FDCs). It has been hypothesized that FDCs are involved in the regulation of B-cell growth and differentiation through cell-cell interactions. In this study, highly enriched preparations of FDCs were isolated by cell sorting using the FDC restricted monoclonal antibody DRC-1. When irradiated FDCs were cultured with mitogen stimulated B cells, B cell 3H-TdR uptake was inhibited by up to 80%. This inhibitory effect was not seen when paraformaldehyde fixed FDCs were added to B-cell cultures, suggesting that the FDCs needed to be metabolically active. Moreover, supernatants from cultured FDCs were similarly able to inhibit B-cell proliferation. These results demonstrate that FDCs may downregulate the clonal expansion of B cells that occurs within lymphoid follicles as part of the normal physiologic immune response. Potentially, the loss of the inhibitory role of FDCs in vivo may be of importance in certain infectious and neoplastic processes in which germinal centers are affected.
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Freedman, AS, JM Munro, K. Rhynhart, P. Schow, J. Daley, N. Lee, J. Svahn, L. Eliseo, and LM Nadler. "Follicular dendritic cells inhibit human B-lymphocyte proliferation." Blood 80, no. 5 (September 1, 1992): 1284–88. http://dx.doi.org/10.1182/blood.v80.5.1284.bloodjournal8051284.
Full textAbstract:
In germinal centers, B lymphocytes are intimately associated with follicular dendritic cells (FDCs). It has been hypothesized that FDCs are involved in the regulation of B-cell growth and differentiation through cell-cell interactions. In this study, highly enriched preparations of FDCs were isolated by cell sorting using the FDC restricted monoclonal antibody DRC-1. When irradiated FDCs were cultured with mitogen stimulated B cells, B cell 3H-TdR uptake was inhibited by up to 80%. This inhibitory effect was not seen when paraformaldehyde fixed FDCs were added to B-cell cultures, suggesting that the FDCs needed to be metabolically active. Moreover, supernatants from cultured FDCs were similarly able to inhibit B-cell proliferation. These results demonstrate that FDCs may downregulate the clonal expansion of B cells that occurs within lymphoid follicles as part of the normal physiologic immune response. Potentially, the loss of the inhibitory role of FDCs in vivo may be of importance in certain infectious and neoplastic processes in which germinal centers are affected.
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Brent, L. H., J. L. Butler, W. T. Woods, and J. K. Bubien. "Transmembrane ion conductance in human B lymphocyte activation." Journal of Immunology 145, no. 8 (October 15, 1990): 2381–89. http://dx.doi.org/10.4049/jimmunol.145.8.2381.
Full textAbstract:
Abstract Human B lymphocytes were examined to determine whether transmembrane ion conductance plays a role in cell activation. Mitogens (anti-human IgM F(ab')2 fragment (anti-mu) and PMA) were used to stimulate B lymphocytes. Mitogen-induced DNA synthesis was inhibited by tetraethylammonium-Cl (TEA), 4-aminopyridine (4AP), verapamil, and diltiazem in a dose-dependent manner. This inhibition was not due to reduction in cell viability as determined by trypan blue exclusion. Mitogen-induced increases in RNA synthesis were partially inhibited by TEA and 4AP and were more completely inhibited by verapamil and diltiazem. Mitogen-induced cell volume increases were not affected by TEA or 4AP but were completely inhibited by verapamil and diltiazem. B lymphocytes stimulated with anti-mu expressed G1 phase cell surface antigens in the presence of TEA or 4AP, but failed to do so in the presence of verapamil or diltiazem. Substitution of PMA for anti-mu as the mitogen did not alter the effects of TEA or 4AP. However, verapamil inhibited PMA-induced expression of G1 phase cell surface markers although diltiazem did not. The patch clamp technique was used to directly examine plasma membrane ionic currents in whole-cell, cell-attached, and inside-out patch configurations. Activation of B lymphocytes with either anti-mu or the Ca2+ ionophore, A23187, inhibited opening of one type of channel in cell-attached patches. In inside-out patches, this channel type conducted current when the bath [Ca2+] was low (6 X 10(-8) M) but failed to conduct current when the bath [Ca2+] was increased above 1 X 10(-6) M. The results of these experiments are consistent with the hypothesis that activation of B lymphocytes induces alterations in plasma membrane ion conductance. Single channel studies suggest that activation induced increases in [Ca2+]i may directly inhibit a specific set of plasma membrane ion channels as one mechanism by which transmembrane ion flux is altered.
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Chan, M. A., L. D. Stein, H. M. Dosch, and N. H. Sigal. "Heterogeneity of EBV-transformable human B lymphocyte populations." Journal of Immunology 136, no. 1 (January 1, 1986): 106–12. http://dx.doi.org/10.4049/jimmunol.136.1.106.
Full textAbstract:
Abstract Although most human B cells express receptors for Epstein Barr virus (EBV), few (usually less than 1%) are readily transformed into B lymphoblastoid cell lines after exposure to EBV. Transformable cells previously have been found to be mostly resting B lymphocytes. We recently developed a limiting dilution culture system which permits the growth of EBV-transformed B lymphocytes with high efficiency. Because in this system up to over 30% of peripheral blood- or tonsil-derived B cells respond to EBV, we re-examined the properties of EBV-transformable cells. Frequencies of transformable lymphocytes were determined by Poisson analysis. EBV-susceptible B cells committed to IgM, IgG, or IgA secretion were found to occur in the range of 3 to 27, 0.1 to 6, and 0.1 to 5 per 100 B cells, respectively. Under our culture conditions, a major proportion of the IgM-committed cells derived from large lymphocytes which appeared to have entered the cell cycle. This population contains most of the EBV-responsive cells detected and, therefore, most of the additional cells responding in our culture system. In contrast, precursors of IgG- or IgA-producing lymphoblast lines were small cells with DNA contents typical for the G0/G1 phases of the cell cycle. Anti-immunoglobulin antibodies were used in panning experiments to separate B cell subpopulations which expressed different immunoglobulin isotypes on their surface. In limiting dilution cultures of these purified B lymphocytes subsets, it was found that virtually all precursors of IgM-producing cell lines expressed surface IgM (sIgM) before their infection and transformation by EBV. The "cloning efficiency" of positively selected, large sIgM+ cells approached 100%. In contrast, sIgG or sIgA were found only on cells committed to the production of IgG or IgA, respectively. The expression of sIgD was examined by using sequential panning procedures. Virtually all IgM-committed lymphocytes and a subset of cells committed to IgA secretion were found among the sIgD+ cells. The majority of cells committed to IgA production and all IgG-committed cells were found in the sIgD- B cell population. Our findings indicate that the EBV-susceptible B cell subset of normal lymphocytes is heterogeneous with respect to cell size, cell cycle, sIg determinants, and efficiency of transformation. On the basis of our findings and previous reports, we propose a model in which transformability is a B cell-inherent property. Factors unrelated to the virus but present in our culture system appear responsible for the enhanced vulnerability to viral transformation in some cells which entered into the cell cycle.(ABSTRACT TRUNCATED AT 400 WORDS)
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Buck, J., F. Grün, F. Derguini, Y. Chen, S. Kimura, N. Noy, and U. Hämmerling. "Anhydroretinol: a naturally occurring inhibitor of lymphocyte physiology." Journal of Experimental Medicine 178, no. 2 (August 1, 1993): 675–80. http://dx.doi.org/10.1084/jem.178.2.675.
Full textAbstract:
Vitamin A (retinol) is an essential cofactor for growth of B lymphocytes in culture and for activation of T lymphocytes by antigen receptor-mediated signals. 14-hydroxy-4,14-retro-retinol (14-HRR) a metabolite of retinol, has been implicated as the intracellular mediator of this effect. Anhydroretinol (AR) is a retinol derivative with retro structure produced in activated human B lymphocytes and the insect cell lines SF 21 and Schneider S2. AR reversibly inhibits retinol- and 14-HRR-dependent effects and blocks B lymphocyte proliferation as well as activation of resting T lymphocytes. The intracellular signaling pathway blocked by AR in T cell activation is distinct from the calcineurin/interleukin 2 pathway inhibitable by cyclosporine A or FK-506.
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Azuma, Hiroshi, Kenji Ikebuchi, Miki Yamaguchi, Hideaki Murahashi, Yuko Mogi, Norihiro Sato, Mitsuhiro Fujihara, Fumiya Hirayama, and Hisami Ikeda. "Comparison of sensitivity to ultraviolet B irradiation between human lymphocytes and hematopoietic stem cells." Blood 96, no. 7 (October 1, 2000): 2632–34. http://dx.doi.org/10.1182/blood.v96.7.2632.
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Abstract To investigate the clinical applicability of prophylaxis of post-transplant graft-versus-host disease by UV-B irradiation of stem cell preparations, the UV-B sensitivities of human lymphocytes and primitive hematopoietic progenitors were compared. The mononuclear cell fractions (MNC) derived from human cord blood and granulocyte–colony-stimulating factor–mobilized peripheral blood were used. After UV-B irradiation, lymphocyte proliferation ability, hematopoietic colony-forming cells, and apoptotic cells were analyzed. At a dose of 33 J/m2, significant differences were observed in the residual percentages of hematopoietic progenitors and lymphocyte functions [ANOVA, F (5,46) = 19.4; P < .0001], and the difference between CFU-C (85.2% + 24.0%; n = 8) and MLR (12.7% + 12.6%; n = 10) was significant (P < .0001). There were no significant differences in the residual percentages of CFU-C, HPP-CFC, and LTC-IC. Percentages of annexin V-positive cells in the total MNC and the CD34+cell population in MNC after UV-B irradiation were 69.8% and 18.7%, respectively. In conclusion, there was a range of UV-B doses over which T lymphocytes were inactivated but hematopoietic progenitors, including HPP-CFC and LTC-IC, were preserved.
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Azuma, Hiroshi, Kenji Ikebuchi, Miki Yamaguchi, Hideaki Murahashi, Yuko Mogi, Norihiro Sato, Mitsuhiro Fujihara, Fumiya Hirayama, and Hisami Ikeda. "Comparison of sensitivity to ultraviolet B irradiation between human lymphocytes and hematopoietic stem cells." Blood 96, no. 7 (October 1, 2000): 2632–34. http://dx.doi.org/10.1182/blood.v96.7.2632.h8002632_2632_2634.
Full textAbstract:
To investigate the clinical applicability of prophylaxis of post-transplant graft-versus-host disease by UV-B irradiation of stem cell preparations, the UV-B sensitivities of human lymphocytes and primitive hematopoietic progenitors were compared. The mononuclear cell fractions (MNC) derived from human cord blood and granulocyte–colony-stimulating factor–mobilized peripheral blood were used. After UV-B irradiation, lymphocyte proliferation ability, hematopoietic colony-forming cells, and apoptotic cells were analyzed. At a dose of 33 J/m2, significant differences were observed in the residual percentages of hematopoietic progenitors and lymphocyte functions [ANOVA, F (5,46) = 19.4; P < .0001], and the difference between CFU-C (85.2% + 24.0%; n = 8) and MLR (12.7% + 12.6%; n = 10) was significant (P < .0001). There were no significant differences in the residual percentages of CFU-C, HPP-CFC, and LTC-IC. Percentages of annexin V-positive cells in the total MNC and the CD34+cell population in MNC after UV-B irradiation were 69.8% and 18.7%, respectively. In conclusion, there was a range of UV-B doses over which T lymphocytes were inactivated but hematopoietic progenitors, including HPP-CFC and LTC-IC, were preserved.
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Liamin, Marie, Hélène Le Mentec, Bertrand Evrard, Laurence Huc, Frédéric Chalmel, Elisa Boutet-Robinet, Eric Le Ferrec, and Lydie Sparfel. "Genome-Wide Transcriptional and Functional Analysis of Human T Lymphocytes Treated with Benzo[α]pyrene." International Journal of Molecular Sciences 19, no. 11 (November 17, 2018): 3626. http://dx.doi.org/10.3390/ijms19113626.
Full textAbstract:
Polycyclic aromatic hydrocarbons (PAHs) are widely distributed environmental contaminants, known to affect T lymphocytes. However, the molecular targets and pathways involved in their immunotoxic effects in human T lymphocytes remain unknown. Here, we analyzed the gene expression profile of primary human T lymphocytes treated with the prototypical PAH, benzo[α]pyrene (B[α]P), using a microarray-based transcriptome analysis. After a 48 h exposure to B[α]P, we identified 158 genes differentially expressed in T lymphocytes, including not only genes well-known to be affected by PAHs such as the cytochromes P450 (CYP) 1A1 and 1B1, but also others not previously shown to be targeted by B[α]P such as genes encoding the gap junction beta (GJB)-2 and 6 proteins. Functional enrichment analysis revealed that these candidates were significantly associated with the aryl hydrocarbon (AhR) and interferon (IFN) signaling pathways; a marked alteration in T lymphocyte recruitment was also observed. Using functional tests in transwell migration experiments, B[α]P was then shown to significantly decrease the chemokine (C-X-C motif) ligand 12-induced chemotaxis and transendothelial migration of T lymphocytes. In total, this study opens the way to unsuspected responsive pathway of interest, i.e., T lymphocyte migration, thus providing a more thorough understanding of the molecular basis of the immunotoxicity of PAHs.
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Baeker, T. R., and T. L. Rothstein. "Proliferation of human malignant lymphocytes induced by anti-IgM independent of B cell growth factor." Journal of Immunology 134, no. 5 (May 1, 1985): 3532–38. http://dx.doi.org/10.4049/jimmunol.134.5.3532.
Full textAbstract:
Abstract Human malignant B lymphocytes were identified that proliferate in response to small doses of anti-immunoglobulin. Proliferation was induced by monoclonal mouse anti-HIgM, polyclonal goat anti-HIgM, and F(ab')2 fragments thereof, in vitro, and was not accompanied by immunoglobulin secretion. Proliferation was found to be unaffected by T cell depletion and was not enhanced by supplementation with B cell growth factor. Culture fluids from unstimulated malignant lymphocytes as well as from malignant lymphocytes stimulated with anti-HIgM contained no measurable B cell growth factor activity. Thus, proliferation of these malignant lymphocytes was not dependent on the presence of T lymphocytes and was independent of the presence of B cell growth factor. These results imply that B cell stimulatory factors may not be required for proliferation of all human B lymphocytes. Moreover, these results imply that treatment with anti-immunoglobulin reagents may be inappropriate for some B lymphocyte malignancies.
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van Schoonhoven, Anne, Danny Huylebroeck, Rudi W. Hendriks, and Ralph Stadhouders. "3D genome organization during lymphocyte development and activation." Briefings in Functional Genomics 19, no. 2 (December 10, 2019): 71–82. http://dx.doi.org/10.1093/bfgp/elz030.
Full textAbstract:
Abstract Chromosomes have a complex three-dimensional (3D) architecture comprising A/B compartments, topologically associating domains and promoter–enhancer interactions. At all these levels, the 3D genome has functional consequences for gene transcription and therefore for cellular identity. The development and activation of lymphocytes involves strict control of gene expression by transcription factors (TFs) operating in a three-dimensionally organized chromatin landscape. As lymphocytes are indispensable for tissue homeostasis and pathogen defense, and aberrant lymphocyte activity is involved in a wide range of human morbidities, acquiring an in-depth understanding of the molecular mechanisms that control lymphocyte identity is highly relevant. Here we review current knowledge of the interplay between 3D genome organization and transcriptional control during B and T lymphocyte development and antigen-dependent activation, placing special emphasis on the role of TFs.
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Tedder, T. F., L. T. Clement, and M. D. Cooper. "Human lymphocyte differentiation antigens HB-10 and HB-11. I. Ontogeny of antigen expression." Journal of Immunology 134, no. 5 (May 1, 1985): 2983–88. http://dx.doi.org/10.4049/jimmunol.134.5.2983.
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Abstract T, B, and NK cells appear to represent separate lymphocyte lineages, but indirect evidence suggests that they may be related via a common lymphoid precursor cell. We have produced two monoclonal antibodies, HB-10 (IgM) and HB-11 (IgG1), by fusing spleen cells from mice immunized with the human B cell line SB, and have shown that both antibodies react with lymphocyte-specific cell surface antigens present on T, B, and NK cells, but not on other types of blood cells. The antibodies were reactive with most cell lines and malignancies of B cell origin and with some of T and NK cell lineage. Although the populations of cells expressing these two antigens were virtually identical, the HB-10 and HB-11 antibodies identified separate protease-sensitive determinants on the cell surface. The HB-11 antigenic determinant was also sensitive to neuraminidase and periodate treatments, but the HB-10 determinant was not. Antigen expression by lymphocytes from fetal, newborn, and adult tissues was examined. Within the B cell lineage, these antigens were expressed by most pre-B cells in bone marrow (88% +/- 5) and almost all B cells, but were not expressed by mature plasma cells. Virtually all of the granular lymphocytes in blood marked by the Leu-7 and Leu-11 (anti-Fc receptor) antibodies were HB-10+ and 11+. Among T lineage cells, the HB-10 and 11 antigens were expressed by a subset of relatively mature T3+ thymocytes and by greater than 90% of the T cells in newborn blood. In adults, however, only 65% of blood T cells and 24 to 30% of splenic or tonsillar T cells expressed the HB-10 and HB-11 antigens. The postnatal emergence of T cells which, like plasma cells, do not express these antigens suggests that post-thymic T lymphocyte maturation occurs and may be an activation-dependent process.
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Gelfand, E. W., and R. Or. "Charybdotoxin-sensitive, Ca(2+)-dependent membrane potential changes are not involved in human T or B cell activation and proliferation." Journal of Immunology 147, no. 10 (November 15, 1991): 3452–58. http://dx.doi.org/10.4049/jimmunol.147.10.3452.
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Abstract The involvement of ion channels in B and T lymphocyte activation is supported by many reports of changes in ion fluxes and membrane potential after mitogen binding. Human T and B lymphocytes demonstrate an early and transient hyperpolarization after ligand binding. Inasmuch as the change in membrane potential is dependent on elevation of free cytosolic calcium, the hyperpolarization is presumably through opening of Ca(2+)-stimulated K+ channels. We have used charybdotoxin, a known inhibitor of Ca(2+)-dependent K+ channels, to study the role of these channels in lymphocyte activation and mitogenesis. We demonstrate that charybdotoxin inhibits the ligand-induced transient membrane hyperpolarization in B and T cells in a dose-dependent fashion, without affecting changes in cytosolic Ca2+. However, blockade of the Ca(2+)-activated K+ channel is not associated with changes in cell-cycle gene activation, IL-2 production, IL-2R expression or B and T cell mitogenesis. These results imply that membrane potential changes secondary to the ligand-dependent opening of Ca(2+)-activated K+ channels are not involved in B and T lymphocyte activation and mitogenesis.
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Bonnaure, Guillaume, and Sonia Néron. "N-acetylcysteine modulation of JAK2 and JAK3 results in decreased STAT3 activation in human B lymphocytes (P1473)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 174.20. http://dx.doi.org/10.4049/jimmunol.190.supp.174.20.
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Abstract Activation of STAT3 is crucial for human B lymphocyte differentiation and inhibition of its phosphorylation in CD40-activated B lymphocytes results in impairment of in vitro generation of immunoglobulin-secreting cells. Conversely, redox homeostasis plays a role in B lymphocyte maturation. Thus, the presence of antioxidants can potentially modulate their outcome. We showed that N-acetylcysteine (NAC), an antioxidant molecule, can inhibit STAT3 phosphorylation, which is paralleled with strong inhibition of immunoglobulins secretion. Western analysis reveals that NAC-treatment of CD40-activated human B lymphocytes, in the presence of IL-2, IL-4 and IL-10, causes a reduced phosphorylation of JAK2 and JAK3, which are important activators of STAT3. Furthermore, this inhibition appears to be dose-dependant. Our results indicate that other antioxidant molecule such as α-tocopherol and trolox do not affect these two kinases phosphorylation. Other kinases or their inhibitors associated to STAT3 phosphorylation do not seem affected by the presence of antioxidant in the media. In conclusion, these observations reveal that STAT3 phosphorylation down regulation in NAC conditions is due to its association with JAK2 and JAK3.
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Miyake, K., K. Medina, K. Ishihara, M. Kimoto, R. Auerbach, and P. W. Kincade. "A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture." Journal of Cell Biology 114, no. 3 (August 1, 1991): 557–65. http://dx.doi.org/10.1083/jcb.114.3.557.
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Two new mAbs (M/K-1 and M/K-2) define an adhesion molecule expressed on stromal cell clones derived from murine bone marrow. The protein is similar in size to a human endothelial cell adhesion molecule known as VCAM-1 or INCAM110. VCAM-1 is expressed on endothelial cells in inflammatory sites and recognized by the integrin VLA-4 expressed on lymphocytes and monocytes. The new stromal cell molecule is a candidate ligand for the VLA-4 expressed on immature B lineage lymphocytes and a possible homologue of human VCAM-1. We now report additional similarities in the distribution, structure, and function of these proteins. The M/K antibodies detected large cells in normal bone marrow, as well as rare cells in other tissues. The antigen was constitutively expressed and functioned as a cell adhesion molecule on cultured murine endothelial cells. It correlated with the presence of mRNA which hybridized to a human VCAM-1 cDNA probe. Partial NH2 terminal amino acid sequencing of the murine protein revealed similarities to VCAM-1 and attachment of human lymphoma cells to murine endothelial cell lines was inhibited by the M/K antibodies. All of these observations suggest that the murine and human cell adhesion proteins may be related. The antibodies selectively interfered with B lymphocyte formation when included in long term bone marrow cultures. Moreover, they caused rapid detachment of lymphocytes from the adherent layer when added to preestablished cultures. The VCAM-like cell adhesion molecule on stromal cells and VLA-4 on lymphocyte precursors may both be important for B lymphocyte formation.
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Michel, Laure, Camille Grasmuck, Marc Charabati, Marc-André Lécuyer, Stephanie Zandee, Tessa Dhaeze, Jorge I. Alvarez, et al. "Activated leukocyte cell adhesion molecule regulates B lymphocyte migration across central nervous system barriers." Science Translational Medicine 11, no. 518 (November 13, 2019): eaaw0475. http://dx.doi.org/10.1126/scitranslmed.aaw0475.
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The presence of B lymphocyte–associated oligoclonal immunoglobulins in the cerebrospinal fluid is a classic hallmark of multiple sclerosis (MS). The clinical efficacy of anti-CD20 therapies supports a major role for B lymphocytes in MS development. Although activated oligoclonal populations of pathogenic B lymphocytes are able to traffic between the peripheral circulation and the central nervous system (CNS) in patients with MS, molecular players involved in this migration have not yet been elucidated. In this study, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM/CD166) identifies subsets of proinflammatory B lymphocytes and drives their transmigration across different CNS barriers in mouse and human. We also showcased that blocking ALCAM alleviated disease severity in animals affected by a B cell–dependent form of experimental autoimmune encephalomyelitis. Last, we determined that the proportion of ALCAM+ B lymphocytes was increased in the peripheral blood and within brain lesions of patients with MS. Our findings indicate that restricting access to the CNS by targeting ALCAM on pathogenic B lymphocytes might represent a promising strategy for the development of next-generation B lymphocyte–targeting therapies for the treatment of MS.
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Grossman, William J., James W. Verbsky, Benjamin L. Tollefsen, Claudia Kemper, John P. Atkinson, and Timothy J. Ley. "Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells." Blood 104, no. 9 (November 1, 2004): 2840–48. http://dx.doi.org/10.1182/blood-2004-03-0859.
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Abstract Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the perforin/granzyme pathway as a major mechanism to kill pathogen-containing cells and tumor cells.1,2 Dysregulation of this pathway results in several human diseases, such as hemophagocytic lymphohistiocytosis. Here we characterize the single-cell expression pattern of granzymes A and B in human lymphocytes using a flow cytometry-based assay. We demonstrate that most circulating CD56+8- NK cells, and approximately half of circulating CD8+ T lymphocytes, coexpressed both granzymes A and B. In contrast, few circulating CD4+ T lymphocytes expressed granzymes A or B. Activation of CD8+ T lymphocytes with concanavalin A (ConA)/interleukin-2 (IL-2), and activation of CD4+ T lymphocytes with antibodies to CD3/CD28 or CD3/CD46 (to generate T regulatory [Tr1] cells), induced substantial expression of granzyme B, but not granzyme A. Naive CD4+CD45RA+ cells stimulated with antibodies to CD3/CD46 strongly expressed granzyme B, while CD3/CD28 stimulation was ineffective. Finally, we show that granzyme B-expressing CD4+ Tr1 cells are capable of killing target cells in a perforin-dependent, but major histocompatibility complex (MHC)/T-cell receptor (TCR)-independent, manner. Our results demonstrate discordant expression of granzymes A and B in human lymphocyte subsets and T regulatory cells, which suggests that different granzymes may play unique roles in immune system responses and regulation.
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Kasaian, M. T., H. Ikematsu, and P. Casali. "Identification and analysis of a novel human surface CD5- B lymphocyte subset producing natural antibodies." Journal of Immunology 148, no. 9 (May 1, 1992): 2690–702. http://dx.doi.org/10.4049/jimmunol.148.9.2690.
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Abstract The production of "natural" autoantibodies or antibodies, i.e., Ig that bind a variety of self- and/or exogenous Ag and arise independently of known immunization, is though to be a feature of CD5+ B lymphocytes. To determine whether other lymphocyte subsets exist that might be committed to the production of natural antibodies, human peripheral blood B cells were sorted on the basis of surface CD5 expression and differential expression of surface CD45RA (CD5+CD45RAintermediate(int), CD5-CD45RAlow(lo), and CD5-CD45RAhigh(hi)), and analyzed for the type of Ig produced after EBV infection and culture. Like their CD5+ counterparts, most CD5-CD45RAlo B lymphocytes were precursors of cells producing IgM, a major proportion of which displayed the Ag-binding features of natural antibodies. In contrast, CD5-CD45RAhi B cells comprised a high frequency of IgG-producing cell precursors, possibly including memory B lymphocytes. Six of seven IgM mAb generated from sorted CD5-CD45RAlo B cells and three of four IgM mAb from sorted CD5+ B cells were polyreactive, binding with different affinities (Kd, 10(-5) to 10(-8) M) to two or more Ag; the remaining mAb from CD5-CD45RAlo and the mAb from CD5+ B cells each bound to a single Ag (Kd, 10(-7) to 10(-8) M), beta-galactosidase and ssDNA, respectively. CD5-CD45RAlo B cells account for 4.1 +/- 1.2% (mean +/- SD in 11 healthy subjects; CD5+ B cells, 23.3 +/- 6.9%) of total B lymphocytes and display the features of quiescent cells. In a given individual, the number of CD5-CD45RAlo B cells remains constant over time. CD5-CD45RAlo and CD5+ B cells bear surface CD11b and CD14, at densities and/or frequencies apparently higher than those of CD5-CD45RAhi B lymphocytes. Despite their surface CD5- phenotype, CD45RAlo B cells express CD5+ mRNA at levels comparable with those of CD5+ B lymphocytes, whereas CD5-CD45RAhi B cells express only trace amounts of CD5 mRNA. The commitment to natural antibody production and the degree of CD5 mRNA expression suggest that the newly defined CD5-CD45RAlo B cell subset is related to CD5+ B lymphocytes, and may constitute the human homologue of the mouse Ly-1-"sister" B cell population.
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Ford, RJ, NM Kouttab, CG Sahasrabuddhe, FM Davis, and SR Mehta. "Growth factor-mediated proliferation in B cell non-Hodgkin's lymphomas." Blood 65, no. 6 (June 1, 1985): 1335–41. http://dx.doi.org/10.1182/blood.v65.6.1335.bloodjournal6561335.
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Abstract The non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of human lymphoid tumors, primarily of B cell lineage, which appear to represent arrested stages in B lymphocyte differentiation. Control of cell proliferation is a fundamentally important but poorly understood area of study in these tumors. We have studied a representative group of B cell NHLs to assess their potential for growth factor-mediated proliferation in vitro. Our results show that purified monoclonal NHL B cells of the small cell (well-differentiated lymphocytic lymphoma, nodular poorly differentiated lymphocytic lymphoma, etc) type, that were positive for the human malignancy-associated nucleolar antigen could be stimulated by human B cell growth factor (BCGF) to proliferate in vitro. Other B cell activators such as insoluble anti-Ig and the mitogen protein A also could stimulate thymidine incorporation in the lymphoma cell populations. In vitro lymphoma cell growth could be maintained in the presence of the growth factor for up to five weeks. The large B cell type NHL, however, appeared to be refractory to in vitro stimulation by BCGF as well as other stimulators of normal B cells. These studies suggest that human B cell lymphoid tumors are not only phenotypically similar to their normal B lymphocyte counterparts, but are also sensitive in some cases, to the same types of immunoregulatory molecules that control normal lymphoid cell growth.
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Singh, Amit K., Roshni Roy, Mary Kaileh, Dimitra Sarantopoulou, Dena Hernandez, Sampath Arepalli, Arsun Bektas, et al. "Unique and shared molecular features of human B and T lymphocyte memory differentiation." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 168.11. http://dx.doi.org/10.4049/jimmunol.208.supp.168.11.
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Abstract Long-term immunity against infections and effective response to vaccination are dependent on remarkable and unique feature of lymphocytes referred as “memory generation”. Despite having multiple mice studies focused on naïve to memory transition of lymphocytes our understanding of human naïve and memory properties is limited. In this study we explored epigenetics (DNA methylation and accessible chromatin), transcriptomics and activation induced gene expression of FACS sorted naïve and memory subsets of B, CD4 T and CD8 T lymphocytes of healthy donors from GESTALT cohort. Shared and specific methylomes between B and T lymphocyte subsets were identified. The relationship between DNA methylation, chromatin accessibility and transcriptome through ATAC-Seq and RNA-Seq data from the same donors is established. Through in-silico analyses and by utilizing data from Roadmap Epigenomics project and ChromHMM, we further identified differentiation-specific connections between DNA methylation, chromatin accessibility, and histone modifications. Transcription factor motif analyses identifies presence of ARNT, OCT and NF-κB motifs around sites hypomethylated in B memory while ETS motifs are in memory-associated hyper-methylated sites. Interestingly, OCT motifs were also significantly enriched in B memory specific accessible chromatin. To understand the extent to which these epigenetic changes effected lymphocytes, we activated naïve and memory subsets of B and CD4+ T lymphocytes in vitro and assayed early and late gene expression changes. These findings will provide the foundation for future studies related to dysregulation of memory cell differentiation in aging and infections. Supported by Intramural Research Program of the National Institute on Aging.
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Xue, Qun, Zhou Yin, Nagam Varshithreddy, Han-si Liang, Ming-yuan Wang, Wan-li Dong, Xueguang Zhang, Yanzheng Gu, and Qi Fang. "The immunomodulatory function of human amniotic fluid stromal cells on B lymphocytes." Journal of Neurorestoratology 1, no. 1 (2018): 122–33. http://dx.doi.org/10.26599/jnr.2018.9040010.
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Current treatments for B cell-mediated disease are mainly based on global B cell depletion, thereby eliminating pathogenic B cells as well as Breg subsets. A more refined modulation of B cell activity could prove beneficial for patient treatment.Objective:To investigate the immunomodulatory function of human amniotic fluid stromal cells (hAFSCs) on different subpopulation of B lymphocytes.Methods:hAFSCs were isolated and cultured and identified by characteristic phenotypic markers. After coculture of B lymphocytes with hAFSCs, the activation, proliferation, differentiation, as well as apoptosis, cell cycle, and expression of the inhibitory costimulatory molecules B7H1, B7H3, and B7H4 of B lymphocytes were examined in vitro.Results:Coculture with hAFSCs significantly decreased the expression of CD80/CD86, Ki-67 and CFSE expression, on activated B lymphocytes. These might be due to the inhibition of B lymphocyte apoptosis and cell cycle arrest. In activated B lymphocytes, coculture with hAFSCs resulted in a reduced proportion of memory B and plasma cells, reduced amounts of immunoglobulins. hAFSCs could balance the B1 to B2 cell subpopulation ratio. hAFSCs could inhibit the expression of the negative co-inhibitory molecule B7H4 and PD-L1 on the activated B lymphocytes.Conclusion:hAFSCs could inhibit B cell activation, proliferation, and subpopulation differentiation. These might be due to their affect on B cell apoptosis, cell cycle and the expression of costimulatory molecules of human B lymphocytes. Our experiment provided the evidence for hAFSCs as ideal seed cells with therapeutic potential for treating humoral immunity disorders, which were mainly mediated by B lymphocytes.