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Journal articles on the topic 'Cencer cells'

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Author: Grafiati

Published: 6 September 2023

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1

Novikova, Inna Arnoldovna, Galina Nerodo, and Anna Iurievna Mordan. "Comparative analysis of DNA-cytometric indices of primary and relapsing ovarian cencer." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e16558-e16558. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e16558.

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e16558 Background: A ploidy of an average grade of aneuploidy cells and of proliferation index in ovarian tumor was studied. Methods: 21 patients with ovarian cancer of III-IV grades and 12 patients with acknowledged relapse of the disease aged from 46 to 67 to part in the research. We used CycleTEST PLUS DNA Reagent Kit (Becton Dickinson) for the analysis of DNA in the tumor’s tissues. Preparation of the tumor’s tissues was made with the use of disaggregating device BD Medimachine; after painting with propidium iodide (PI) we analyzed at flow cytofluorimeter BD Facs CantooII. Received data was processed with the help of computer program ModFit LT, allowing to analyze the ploidy and distribution of tumor’s cells according to phases of cellular cycle. Results: There was revealed the 2.5 times predominance of aneuploidy tumors over diploid in case of the relapse of the disease. The DNA index, different from 1.0, was registered in 83.3%, whereas there was noticed 33.3% primary ovarian tumors with aneuploidy content of DNA with predominance of diploidy tumors. There was noticed a tendency to the increase of aneuploidy cells during the relapse of the disease, where they made up 42.7±1.8%, whereas in primary ovarian tumors the share of aneuploidy cells was 40.4±1.6%. The index of proliferation of relapsing tumors was 1.8 times higher than this index of primary tumors, and made up 35.5±2.9 and 26.7±2.1 (p < 0.05). Conclusions: During the relapse of a tumor there is a predominance of aneuploidy tumors over diploid, the index of proliferation is higher in comparison with primary tumors.

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2

Wang, Huishan, Yan wen Liu, and Lin Miao. "Su2018 – Long Non-Coding Rna Zfas1 Promotes Proliferation of Colorectal Cencer Cells Via Upregulation Srebp1C to Promote De Novo Lipogenesis." Gastroenterology 156, no. 6 (May 2019): S—691—S—692. http://dx.doi.org/10.1016/s0016-5085(19)38650-0.

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3

Hamel, Keith M., Vladimir M. Liarski, and Marcus R. Clark. "Germinal Center B-cells." Autoimmunity 45, no. 5 (April 2, 2012): 333–47. http://dx.doi.org/10.3109/08916934.2012.665524.

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4

LANKHEET, MARTIN J. M., PETER LENNIE, and JOHN KRAUSKOPF. "Distinctive characteristics of subclasses of red–green P-cells in LGN of macaque." Visual Neuroscience 15, no. 1 (January 1998): 37–46. http://dx.doi.org/10.1017/s0952523898151027.

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We characterized the chromatic and temporal properties of a sample of 177 red–green parvocellular neurons in the LGN of Macaca nemestrina, using large-field stimuli modulated along different directions through a white point in color space. We examined differences among the properties of the four subclasses of red–green P-cells (on- and off-center, red and green center). The responses of off-center cells lag the stimulus more than do those of on-center cells. At low temporal frequencies, this causes the phase difference between responses of the two kinds of cells to be considerably less than 180 deg. For isoluminant modulations the phases of on- and off-responses were more nearly 180 deg apart. A cell's temporal characteristics did not depend on the class of cone driving its center. Red center and green center cells have characteristically different chromatic properties, expressed either as preferred elevations in color space, or as weights with which cells combine inputs from L- and M-cones. Red center cells are relatively more responsive to achromatic modulation, and attach relatively more weight to input from the cones driving the center. Off-center cells also attach relatively more weight than do on-center cells to input from the class of cone driving the center.

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5

Glover, Joel C. "From cartilage to cancer: Translational research at the Norwegian Center for Stem Cell Research." Cellular Therapy and Transplantation 4, no. 1-2 (2015): 66–68. http://dx.doi.org/10.18620/1866-8836-2015-4-1-2-66-68.

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6

Hurtley, Stella M., and Kristen L. Mueller. "Guiding immune cells to the center." Science 356, no. 6339 (May 18, 2017): 712.11–714. http://dx.doi.org/10.1126/science.356.6339.712-k.

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7

Zanetti, Maurizio. "Gating on germinal center B cells." Blood 110, no. 12 (December 1, 2007): 3816–17. http://dx.doi.org/10.1182/blood-2007-08-105502.

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8

Butch, A. W., G. H. Chung, J. W. Hoffmann, and M. H. Nahm. "Cytokine expression by germinal center cells." Journal of Immunology 150, no. 1 (January 1, 1993): 39–47. http://dx.doi.org/10.4049/jimmunol.150.1.39.

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Abstract Germinal centers (GC) primarily consist of B cells along with a small number of T cells (5 to 10%) and follicular dendritic cells (FDC) (< or = 1%). Although extensive Ag-driven B cell proliferation and maturation occurs in GC, very little is known about the role of cytokines in the development of GC B cells. Therefore, to identify cytokines present in the GC microenvironment that may influence B cell development, we systematically examined cytokine gene expression by GC cells. GC T cells (CD57+/CD4+), GC B cells (CD77+), and FDC (HJ2+) were isolated from human tonsils by cell sorting using a flow cytometer. Freshly isolated GC cells were examined for mRNA expression for IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, TNF-alpha, and IFN-gamma using reverse transcription polymerase chain reaction. Freshly isolated GC T cells consistently expressed IL-4 mRNA (11 of 12 tonsils), whereas CD57- Th cells (mostly non-GC Th cells) were often negative for IL-4 mRNA. When the other nine cytokine mRNA were studied, freshly isolated CD57+ Th cells occasionally expressed mRNA for IL-10, TNF-alpha, and IFN-gamma. CD57- Th cells were occasionally positive for IL-1 beta, IL-10, IFN-gamma, and TNF-alpha, and negative for IL-2 and IL-6. Freshly isolated GC B cells as well as FDC failed to express detectable quantities of mRNA for all 10 cytokines that were studied. Thus, IL-4 is the only cytokine out of 10 that is consistently expressed in GC and may be important for the development of B cells in GC. After stimulation of CD57+ Th cells with PWM, production of IL-4 mRNA was dramatically reduced, whereas CD57- Th cell production of IL-4 was greatly augmented. This finding indicates that GC T cells may differ from other Th cells in cytokine gene expression and that results of cytokine production obtained after in vitro stimulation do not always reflect in vivo results.

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9

Bowen, Mary B., Anthony W. Butch, Curtis A. Parvin, Alan Levine, and Moon H. Nahm. "Germinal center T cells are distinct helper-inducer T cells." Human Immunology 31, no. 1 (May 1991): 67–75. http://dx.doi.org/10.1016/0198-8859(91)90050-j.

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10

Norman, Helen. "Advice Center." Electric and Hybrid Rail Technology 2022, no. 1 (March 2022): 30–31. http://dx.doi.org/10.12968/s2754-7760(23)70037-6.

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11

Bilotta, J., and I. Abramov. "Spatiospectral properties of goldfish retinal ganglion cells." Journal of Neurophysiology 62, no. 5 (November 1, 1989): 1140–48. http://dx.doi.org/10.1152/jn.1989.62.5.1140.

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1. Responses of single ganglion cells from isolated goldfish retinas were recorded during presentation of various spatial and spectral stimuli. Each cell was classified along several spatial [spatial summation class, spatial contrast sensitivity function (CSF), and response to contrast] and spectral (Red-ON, Red-OFF or Red-ON/OFF, and spectral opponency/nonopponency) dimensions. 2. Linearity of spatial summation was determined from responses to contrast-reversal sinusoidal gratings positioned at various locations across the receptive field of the cell. CSFs were derived from responses to sinusoidal gratings of various spatial frequencies and contrasts, drifting across the cell's receptive field at a rate of 4 Hz. Response to contrast was determined from responses to variations in contrast of a sinusoidal grating of optimal spatial frequency. Spectral classifications were based on responses to monochromatic stimuli presented separately to the center and surround portions of the receptive field. 3. Linearity of spatial summation (X-, Y-, and W-like) was independent of the cell's spectral properties; for example, an X-like cell could be classified as either a Red-ON, Red-OFF, or Red-ON/OFF center cell and as spectrally opponent or nonopponent. 4. There were differences in response to contrast across spectral categories. Red-OFF center cells were very sensitive to contrast compared with Red-ON center cells. Spectrally nonopponent cells were more responsive to contrast than spectrally opponent cells. 5. There were dramatic differences across the spectral categories in relative sensitivity to low spatial frequency stimuli; however, the spatial resolution (i.e., sensitivity to high spatial frequencies) of each spectral classification appeared to be similar.(ABSTRACT TRUNCATED AT 250 WORDS)

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12

Watanabe, Masami, and Yoshihito Tokita. "Difference in regeneration and survival between OFF-center ganglion cells and ON-center cells in cat retina." Neuroscience Research 58 (January 2007): S90. http://dx.doi.org/10.1016/j.neures.2007.06.1091.

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13

Oliver, A. M., F. Martin, and J. F. Kearney. "Mouse CD38 is down-regulated on germinal center B cells and mature plasma cells." Journal of Immunology 158, no. 3 (February 1, 1997): 1108–15. http://dx.doi.org/10.4049/jimmunol.158.3.1108.

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Abstract Germinal center formation is the result of antigenic stimulation of B cells in a T cell-rich area. B cells cycle through the germinal centers, and a small percentage survive to become plasma cells or memory B cells. The transformation from a mature B cell into a germinal center B cell and finally into a terminally differentiated B cell is not well understood. Human CD38 is highly expressed on both germinal center B cells and plasma cells, and is useful in delineating these B cell subsets and in understanding the signaling events involved in the development of these B cells. To determine whether CD38 expression on activated germinal center B cells and postgerminal center B cells influences germinal center differentiation, we studied the expression of CD38 in the mouse. CD38 is expressed on follicular B cells in the Peyer's patches but is down-regulated on germinal center B cells located within the Peyer's patches. CD38dim/-B220+ germinal center B cells are also found in the spleens of immunized but not control mice, suggesting that Ag-stimulated germinal center formation is involved in the production of CD38dim/-B220+ B cells. Furthermore, mature plasma cells isolated from in vitro LPS cultures do not express CD38, but do contain high levels of cytoplasmic Ig. These results are in contrast to studies in humans in which CD38 is not found on follicular B cells but is highly expressed on germinal center B cells and plasma cells.

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14

Frishman, L. J., A. W. Freeman, J. B. Troy, D. E. Schweitzer-Tong, and C. Enroth-Cugell. "Spatiotemporal frequency responses of cat retinal ganglion cells." Journal of General Physiology 89, no. 4 (April 1, 1987): 599–628. http://dx.doi.org/10.1085/jgp.89.4.599.

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Spatiotemporal frequency responses were measured at different levels of light adaptation for cat X and Y retinal ganglion cells. Stationary sinusoidal luminance gratings whose contrast was modulated sinusoidally in time or drifting gratings were used as stimuli. Under photopic illumination, when the spatial frequency was held constant at or above its optimum value, an X cell's responsivity was essentially constant as the temporal frequency was changed from 1.5 to 30 Hz. At lower temporal frequencies, responsivity rolled off gradually, and at higher ones it rolled off rapidly. In contrast, when the spatial frequency was held constant at a low value, an X cell's responsivity increased continuously with temporal frequency from a very low value at 0.1 Hz to substantial values at temporal frequencies higher than 30 Hz, from which responsivity rolled off again. Thus, 0 cycles X deg-1 became the optimal spatial frequency above 30 Hz. For Y cells under photopic illumination, the spatiotemporal interaction was even more complex. When the spatial frequency was held constant at or above its optimal value, the temporal frequency range over which responsivity was constant was shorter than that of X cells. At lower spatial frequencies, this range was not appreciably different. As for X cells, 0 cycles X deg-1 was the optimal spatial frequency above 30 Hz. Temporal resolution (defined as the high temporal frequency at which responsivity had fallen to 10 impulses X s-1) for a uniform field was approximately 95 Hz for X cells and approximately 120 Hz for Y cells under photopic illumination. Temporal resolution was lower at lower adaptation levels. The results were interpreted in terms of a Gaussian center-surround model. For X cells, the surround and center strengths were nearly equal at low and moderate temporal frequencies, but the surround strength exceeded the center strength above 30 Hz. Thus, the response to a spatially uniform stimulus at high temporal frequencies was dominated by the surround. In addition, at temporal frequencies above 30 Hz, the center radius increased.

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15

Lampert, I. A., Susan Van Noorden, and A. C. Wotherspoon. "Centrocytoid Plasma Cells of the Germinal Center." Applied Immunohistochemistry & Molecular Morphology 13, no. 2 (June 2005): 124–31. http://dx.doi.org/10.1097/01.pai.0000135614.30196.fb.

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16

Shepard, Nora, and Nelson Mitchell. "Hyperglycogenic secondary center cells in rat femurs." Proceedings, annual meeting, Electron Microscopy Society of America 46 (1988): 402–3. http://dx.doi.org/10.1017/s0424820100104078.

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The cells forming the secondary center have been described and compared to the hypertrophic chondrocytes of the primary growth plate (ref.I,2). In an attempt to clarify the nature of the vacuolization and associated cell hypertrophy reported to also take place within the chondrocytes of the secondary center prior to the onset of ossification an attempt to improve chondrocyte morphology was made. Glutaraldehyde fixation followed by buffered osmium was compared to tissue fixed with potassium ferrocyanide reduced osmium.Cartilage slices from 5-7 day rats (distal femur) were fixed in 2% glutaraldehyde/0.1M Na phosphate pH 7.4 (2 hrs.); rinsed in 0.1M N phosphate buffer plus 0.1M sucrose (15. min.); post fixed in 1.5% potassium ferrocyanide in aqueous OSO4 or in 2% OSO4/0.1M Na phosphate (2 hrs.); rinsed in 0.1M Na acetate (pH 6.3); en bloc stained in .25% uranyl acetate/0.1M Na acetate; dehydrated in alcohol and Spurr embedded.

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17

Brink, Robert. "Germinal-Center B Cells in the Zone." Immunity 26, no. 5 (May 2007): 552–54. http://dx.doi.org/10.1016/j.immuni.2007.05.002.

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18

Tarlinton, David. "IL-17 drives germinal center B cells?" Nature Immunology 9, no. 2 (February 2008): 124–26. http://dx.doi.org/10.1038/ni0208-124.

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19

Huang, Hao-Jen, David Takagawa, Gerald Weeks, and Catherine Pears. "Cells at the Center ofDictyosteliumAggregates Become Spores." Developmental Biology 192, no. 2 (December 1997): 564–71. http://dx.doi.org/10.1006/dbio.1997.8769.

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20

Han, Shuhua, Biao Zheng, Yoshimasa Takahashi, and Garnett Kelsoe. "Distinctive characteristics of germinal center B cells." Seminars in Immunology 9, no. 4 (August 1997): 255–60. http://dx.doi.org/10.1006/smim.1997.0081.

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21

Kelly, Kathleen A., R. P. Bucy, and Moon H. Nahm. "Germinal Center T Cells Exhibit Properties of Memory Helper T Cells." Cellular Immunology 163, no. 2 (July 1995): 206–14. http://dx.doi.org/10.1006/cimm.1995.1118.

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22

Watanabe, Masami, and Yutaka Fukuda. "Proportions of ON-Center versus OFF-Center Cells in Retinal Ganglion Cells with Regenerated Axons of Adult Cats." Experimental Neurology 143, no. 1 (January 1997): 117–23. http://dx.doi.org/10.1006/exnr.1996.6345.

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23

Airas, L., and S. Jalkanen. "CD73 mediates adhesion of B cells to follicular dendritic cells." Blood 88, no. 5 (September 1, 1996): 1755–64. http://dx.doi.org/10.1182/blood.v88.5.1755.1755.

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Abstract Lymphocyte-vascular adhesion protein-2 was recently identified as CD73. The CD73 molecule, otherwise known as ecto-5′-nucleotidase, is a lymphocyte maturation marker that is involved in intracellular signaling, and lymphocyte proliferation and activation. We now show that CD73, in addition to mediating lymphocyte binding to endothelial cells, also mediates adhesion between B cells and follicular dendritic cells (FDC), as a monoclonal antibody (MoAb) against CD73 inhibited the aggregation of isolated germinal center B cells and FDC in vitro. Cytocentrifuge preparations of isolated germinal center cells and two- color immunofluorescence stainings of different tonsillar B-cell populations show that CD73 is expressed on FDC and on small, recirculating IgD+ B cells, but only on a few B cells inside the germinal center. Thus, we propose that CD73 on FDC has an important role in controlling B cell-FDC interactions and B-cell maturation in germinal centers.

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Airas, L., and S. Jalkanen. "CD73 mediates adhesion of B cells to follicular dendritic cells." Blood 88, no. 5 (September 1, 1996): 1755–64. http://dx.doi.org/10.1182/blood.v88.5.1755.bloodjournal8851755.

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Lymphocyte-vascular adhesion protein-2 was recently identified as CD73. The CD73 molecule, otherwise known as ecto-5′-nucleotidase, is a lymphocyte maturation marker that is involved in intracellular signaling, and lymphocyte proliferation and activation. We now show that CD73, in addition to mediating lymphocyte binding to endothelial cells, also mediates adhesion between B cells and follicular dendritic cells (FDC), as a monoclonal antibody (MoAb) against CD73 inhibited the aggregation of isolated germinal center B cells and FDC in vitro. Cytocentrifuge preparations of isolated germinal center cells and two- color immunofluorescence stainings of different tonsillar B-cell populations show that CD73 is expressed on FDC and on small, recirculating IgD+ B cells, but only on a few B cells inside the germinal center. Thus, we propose that CD73 on FDC has an important role in controlling B cell-FDC interactions and B-cell maturation in germinal centers.

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25

Chen, Shuwen, Masaki Miyazaki, Vivek Chandra, Kathleen M. Fisch, Aaron N. Chang, and Cornelis Murre. "Id3 Orchestrates Germinal Center B Cell Development." Molecular and Cellular Biology 36, no. 20 (July 25, 2016): 2543–52. http://dx.doi.org/10.1128/mcb.00150-16.

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Previous studies have demonstrated that E proteins induce activation-induced deaminase (AID) expression in activated B cells. Here, we examined the role of Id3 in germinal center (GC) cells. We found that Id3 expression is high in follicular B lineage cells but declines in GC cells. Immunized mice with Id3 expression depleted displayed a block in germinal center B cell maturation, showed reduced numbers of marginal zone B cells and class-switched cells, and were associated with decreased antibody titers and lower numbers of plasma cells.In vitro, Id3-depleted B cells displayed a defect in class switch recombination. Whereas AID levels were not altered in Id3-depleted activated B cells, the expression of a subset of genes encoding signaling components of antigen receptor-, cytokine receptor-, and chemokine receptor-mediated signaling was significantly impaired. We propose that during the GC reaction, Id3 levels decline to activate the expression of genes encoding signaling components that mediate B cell receptor- and or cytokine receptor-mediated signaling to promote the differentiation of GC B cells.

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26

Bilotta, Joseph, and Israel Abramov. "Orientation and Direction Tuning of Goldfish Ganglion Cells." Visual Neuroscience 2, no. 1 (January 1989): 3–13. http://dx.doi.org/10.1017/s0952523800004260.

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AbstractOrientation and direction tuning were examined in goldfish ganglion cells by drifting sinusoidal gratings across the receptive field of the cell. Each ganglion cell was first classified as X-, Y- or W-like based on its responses to a contrast-reversal grating positioned at various spatial phases of the cell's receptive field. Sinusoidal gratings were drifted at different orientations and directions across the receptive field of the cell; spatial frequency and contrast of the grating were also varied. It was found that some X-like cells responded similarly to all orientations and directions, indicating that these cells had circular and symmetrical fields. Other X-like cells showed a preference for certain orientations at high spatial frequencies suggesting that these cells possess an elliptical center mechanism (since only the center mechanism is sensitive to high spatial frequencies). In virtually all cases, X-like cells were not directionally tuned. All but one Y-like cell displayed orientation tuning but, as with X-like cells, orientation tuning appeared only at high spatial frequencies. A substantial portion of these Y-like cells also showed a direction preference. This preference was dependent on spatial frequency but in a manner different from orientation tuning, suggesting that these two phenomena result from different mechanisms. All W-like cells possessed orientation and direction tuning, both of which depended on the spatial frequency of the stimulus. These results support past work which suggests that the center and surround components of retinal ganglion cell receptive fields are not necessarily circular or concentric, and that they may actually consist of smaller subareas.

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Saurabh, Vashishtha, Kaushal Devashish, Rawal Sudhir, Joshi Robin, and Khanna Samir. "Safety and Efficacy of Sunitinib for Metastatic Renal Cell Carcinoma in Indian Population: A Tertiary Care Center Experience." New Indian Journal of Surgery 9, no. 4 (2018): 428–32. http://dx.doi.org/10.21088/nijs.0976.4747.9418.5.

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28

Knierim, J. J., and D. C. van Essen. "Neuronal responses to static texture patterns in area V1 of the alert macaque monkey." Journal of Neurophysiology 67, no. 4 (April 1, 1992): 961–80. http://dx.doi.org/10.1152/jn.1992.67.4.961.

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1. We recorded responses from neurons in area V1 of the alert macaque monkey to textured patterns modeled after stimuli used in psychophysical experiments of pop-out. Neuronal responses to a single oriented line segment placed within a cell's classical receptive field (CRF) were compared with responses in which the center element was surrounded by rings of elements placed entirely outside the CRF. The orientations of the surround elements either matched the center element, were orthogonal to it, or were random. 2. The addition of the textured surround tended to suppress the response to the center element by an average of 34%. Overall, almost 80% of the 122 cells analyzed in detail were significantly suppressed by at least one of the texture surrounds. 3. Cells tended to respond more strongly to a stimulus in which there was a contrast in orientation between the center and surround than to a stimulus lacking such contrast. The average difference was 9% of the response to the optimally oriented center element alone. For the 32% of the cells showing a statistically significant orientation contrast effect, the average difference was 28%. 4. Both the general suppression and orientation contrast effects originated from surround regions at the ends of the center bar as well as regions along the sides of the center bar. 5. The amount of suppression induced by the texture surround decreased as the density of the texture elements decreased. 6. Both the general suppression and the orientation contrast effects appeared early in the population response to the stimuli. The general suppression effect took approximately 7 ms to develop, whereas the orientation contrast effect took 18-20 ms to develop. 7. These results are consistent with a possible functional role of V1 cells in the mediation of perceptual pop-out and in the segregation of texture borders. Possible anatomic substrates of the effects are discussed.

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29

Wikenheiser, Daniel J., Florian Weisel, Maria Chikina, and Mark J. Shlomchik. "A germinal center B cell-specific long non-coding RNA regulates the germinal center response." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 151.23. http://dx.doi.org/10.4049/jimmunol.204.supp.151.23.

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Abstract Long non-coding RNAs are a unique class of molecules involved in an exceptional variety of cellular processes, including transcriptional, translational, and epigenetic regulation. Here, we report the initial characterization of a lncRNA expressed specifically in the germinal center--organized sites of B cell proliferation, somatic hyper-mutation, and cellular differentiation that develop in response to antigenic challenge. The precise signals dictating how and when differentiated cells, such as memory B cells and long-lived plasma cells, exit the GC reaction remain incompletely understood. Thus, additional levels of molecular regulation are likely at work in the coordination of these diverse processes. We identify GCLnc1--a novel, nuclear-localized lncRNA--as a regulator of the GC reaction. As GCLnc1 is located adjacent to the murine Bcl6 locus, this lncRNA has the potential to modulate expression of key transcription factors controlling B cell identity and/or differentiation. Interestingly, forced over-expression of GCLnc1 in B cells led to upregulation of TFs associated with plasma cell identity, such as IRF4 and Blimp-1. When adoptively transferred in vivo, over-expression of GCLnc1 led to transduced B cells predominantly adopting a non-GC phenotype at the typical peak GC response, in addition to enhancing expression of IRF4 and Blimp-1. Genetic deletion of GCLnc1 led to reduced frequency of GC B cells, decreased Bcl6 expression, and dysregulated light zone/dark zone distribution in response to NP-KLH immunization. Collectively, we suggest GCLnc1 plays a key role in the integration of signaling events during the GC reaction, and may modulate the processes that drive GC exit.

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30

Quizon, Nicolas, Kihyuck Kwak, Haewon Sohn, and Susan K. Pierce. "Human germinal center B cells are intrinsically distinct from naive B cells." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 52.4. http://dx.doi.org/10.4049/jimmunol.198.supp.52.4.

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Abstract In germinal centers (GCs) B cells undergo cycles of proliferation and somatic hyper mutation followed by affinity discrimination. Selection of GC B cells expressing high affinity B cell receptors (BCRs) is driven by the ability of B cells to signal through the BCR and extract antigen to present to follicular helper T cells. Here we provide evidence that human tonsillar GC B cells, as compared to naïve tonsillar B cells, may have a higher threshold for affinity selection but be better able to interact with T cells and, once triggered through the BCR, may form more stable signaling complexes. A comprehensive quantitative analysis of surface proteins showed distinct profiles for naïve and GC B cells. In particular, GC B cells express less of the integrin VLA-4 and as a consequence were less able to engage beads coated with its ligand, VCAM-1. Given that VLA-4 tethers B cells to VCAM-expressing cell surfaces and facilitates BCR-dependent activation, a reduction in VLA-4 expression would be predicted to raise the threshold for affinity selection in GC B cells. GC B cells also tended to have increased surface expression of proteins that mediate T-B-cell interactions, such as CD80 and CD86, suggesting that once antigen is captured and presented GC B cells would be better equipped to engage helper T cells. To explore BCR signaling we imaged synapses formed between B cells with anti-Ig-containing planar lipid bilayers via total internal reflection fluorescence microscopy. GC B cells tended to form more stable signaling complexes showing greater co-localization between their BCRs and components of their signaling pathway. Taken together these data point toward intrinsic differences between GC and naïve B cells that may contribute to the outcome of GC responses.

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31

Barnett, Burton, Maria Ciocca, Radhika Goenka, Lisa Barnett, Junmin Wu, Terri Laufer, Janis Burkhardt, Michael Cancro, and Steven Reiner. "Asymmetric division of germinal center B cells (109.1)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 109.1. http://dx.doi.org/10.4049/jimmunol.188.supp.109.1.

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Abstract B cells that encode high-affinity, protective antibodies are generated in the germinal center (GC) reaction, a microanatomical structure that includes GC B cells and follicular helper T cells (TFH). The selection of GC B cells to proliferate and differentiate into plasma cells and memory B cells relies on contacts with TFH. In other instances where cells undergo external contacts, polarity cues are imparted that lead to asymmetric division. We hypothesized TFH may provide polarity cues during these interactions, in addition to mitogenic and differentiative signals, so that GC B cells may divide asymmetrically to generate diversity. Using confocal microscopy we observe that GC B cells asymmetrically segregate and unequally inherit the ancestral polarity regulator PKCζ, and the receptor for interleukin 21 (IL-21R) and Bcl6, which are responsible for initiating and maintaining the GC B cell fate, respectively. Homeostatic proliferation does not involve asymmetric divisions, while ICAM-1 and CD40 both contribute to asymmetric division of B cells in vivo and in vitro, respectively. In the absence of asymmetric division, we observe a failure to generate antibody secreting cells from GCs. Together, these data support a model where, in addition to canonical signals, GC B cells receive polarity cues from TFH that result in the unequal inheritance of fate determinants by daughter B cells, leading to divergent differentiation.

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32

Bilotta, J., and I. Abramov. "Spatial properties of goldfish ganglion cells." Journal of General Physiology 93, no. 6 (June 1, 1989): 1147–69. http://dx.doi.org/10.1085/jgp.93.6.1147.

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We systematically classified goldfish ganglion cells according to their spatial summation properties using the same techniques and criteria used in cat and monkey research. Results show that goldfish ganglion cells can be classified as X-, Y-, or W-like based on their responses to contrast-reversal gratings. Like cat X cells, goldfish X-like cells display linear spatial summation. Goldfish Y-like cells, like cat Y cells, respond with frequency doubling at all spatial positions when the contrast-reversal grating consists of high spatial frequencies. There is also a third class of neurons, which is neither X- nor Y-like; many of these cells' properties are similar to those of the "not-X" cells found in the eel retina. Spatial filtering characteristics were obtained for each cell by drifting sinusoidal gratings of various spatial frequencies and contrasts across the receptive field of the cell at a constant temporal rate. The spatial tuning curves of the cell depend on the temporal parameters of the stimulus; at high drift rates, the tuning curves lose their low spatial frequency attenuation. To explore this phenomenon, temporal contrast response functions were derived from the cells' responses to a spatially uniform field whose luminance varied sinusoidally in time. These functions were obtained for the center, the surround, and the entire receptive field. The results suggest that differences in the cells' spatial filtering across stimulus drift rate are due to changes in the interaction of the center and surround mechanisms; at low temporal frequencies, the center and surround responses are out-of-phase and mutually antagonistic, but at higher temporal rates their responses are in-phase and their interaction actually enhances the cell's responsiveness.

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Hare, W. A., and W. G. Owen. "Receptive field of the retinal bipolar cell: a pharmacological study in the tiger salamander." Journal of Neurophysiology 76, no. 3 (September 1, 1996): 2005–19. http://dx.doi.org/10.1152/jn.1996.76.3.2005.

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1. It is widely believed that signals contributing to the receptive field surrounds of retinal bipolar cells pass from horizontal cells to bipolar cells via GABAergic synapses. To test this notion, we applied gamma-aminobutyric acid (GABA) agonists and antagonists to isolated, perfused retinas of the salamander Ambystoma tigrinum while recording intracellularly from bipolar cells, horizontal cells, and photoreceptors. 2. As we previously reported, administration of the GABA analogue D-aminovaleric acid in concert with picrotoxin did not block horizontal cell responses or the center responses of bipolar cells but blocked the surround responses of both on-center and off-center bipolar cells. 3. Surround responses were not blocked by the GABA, antagonists picrotoxin or bicuculline, the GABAB agonist baclofen or the GABAB antagonist phaclofen, and the GABAC antagonists picrotoxin or cis-4-aminocrotonic acid. Combinations of these drugs were similarly ineffective. 4. GABA itself activated a powerful GABA uptake mechanism in horizontal cells for which nipecotic acid is a competitive agonist. It also activated, both in horizontal cells and bipolar cells, large GABAA conductances that shunted light responses but that could be blocked by picrotoxin or bicuculline. 5. GABA, administered together with picrotoxin to block the shunting effect of GABAA activation, did not eliminate bipolar cell surround responses at concentrations sufficient to saturate the known types of GABA receptors. 6. Surround responses were not blocked by glycine or its antagonist strychnine, or by combinations of drugs designed to eliminate GABAergic and glycinergic pathways simultaneously. 7. Although we cannot fully discount the involvement of a novel GABAergic synapse, the simplest explanation of our findings is that the primary pathway mediating the bipolar cell's surround is neither GABAergic nor glycinergic.

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34

Natkunam, Yasodha. "The Biology of the Germinal Center." Hematology 2007, no. 1 (January 1, 2007): 210–15. http://dx.doi.org/10.1182/asheducation-2007.1.210.

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Abstract The immune system requires the production of high affinity antibodies of different subclasses to accomplish its many effector functions. Specific steps in B-cell ontogeny that occur within germinal centers of secondary lymphoid organs create much of the diversity in the immune system. This process also provides the raw material for the genesis of B-cell lymphomas as misdirection of the molecular machinery that regulate these steps can cause chromosomal translocations, prevent apoptosis and promote proliferation of abnormal clones. Many recent avenues of investigation have elucidated that the germinal center is a dynamic microenvironment where B-cells undergo repeated rounds of mutation and selection. Gene expression studies have further shown that malignancies derived from germinal center B-cells elaborate specific gene expression signatures that derive from neoplastic cells as well as elements of the host response such as T-cells and macrophages. This review will examine the current understanding of B-cell development in the germinal center and the key molecules involved in this process. Interactions between lymphoma cells and their cellular partners and models in the growth and development of follicular lymphoma will be presented.

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35

Natkunam, Yasodha. "The Biology of the Germinal Center." Hematology 2007, no. 1 (January 1, 2007): 210–15. http://dx.doi.org/10.1182/asheducation.v2007.1.210.0010210.

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The immune system requires the production of high affinity antibodies of different subclasses to accomplish its many effector functions. Specific steps in B-cell ontogeny that occur within germinal centers of secondary lymphoid organs create much of the diversity in the immune system. This process also provides the raw material for the genesis of B-cell lymphomas as misdirection of the molecular machinery that regulate these steps can cause chromosomal translocations, prevent apoptosis and promote proliferation of abnormal clones. Many recent avenues of investigation have elucidated that the germinal center is a dynamic microenvironment where B-cells undergo repeated rounds of mutation and selection. Gene expression studies have further shown that malignancies derived from germinal center B-cells elaborate specific gene expression signatures that derive from neoplastic cells as well as elements of the host response such as T-cells and macrophages. This review will examine the current understanding of B-cell development in the germinal center and the key molecules involved in this process. Interactions between lymphoma cells and their cellular partners and models in the growth and development of follicular lymphoma will be presented.

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36

Wen, Renren, and Demin Wang. "MCD-DLBCL arises from germinal center B cells." Blood 140, no. 10 (September 8, 2022): 1058–59. http://dx.doi.org/10.1182/blood.2022017534.

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37

Young, Clara, and Robert Brink. "The unique biology of germinal center B cells." Immunity 54, no. 8 (August 2021): 1652–64. http://dx.doi.org/10.1016/j.immuni.2021.07.015.

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38

Schwickert, Tanja A., Boris Alabyev, Tim Manser, and Michel C. Nussenzweig. "Germinal center reutilization by newly activated B cells." Journal of Experimental Medicine 206, no. 13 (November 23, 2009): 2907–14. http://dx.doi.org/10.1084/jem.20091225.

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Germinal centers (GCs) are specialized structures in which B lymphocytes undergo clonal expansion, class switch recombination, somatic hypermutation, and affinity maturation. Although these structures were previously thought to contain a limited number of isolated B cell clones, recent in vivo imaging studies revealed that they are in fact dynamic and appear to be open to their environment. We demonstrate that B cells can colonize heterologous GCs. Invasion of primary GCs after subsequent immunization is most efficient when T cell help is shared by the two immune responses; however, it also occurs when the immune responses are entirely unrelated. We conclude that GCs are dynamic anatomical structures that can be reutilized by newly activated B cells during immune responses.

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39

Peng, Huai-Zheng, Ming-Qing Du, Athanasios Koulis, Antonella Aiello, Ahmet Dogan, Lang-Xing Pan, and Peter G. Isaacson. "Nonimmunoglobulin Gene Hypermutation in Germinal Center B Cells." Blood 93, no. 7 (April 1, 1999): 2167–72. http://dx.doi.org/10.1182/blood.v93.7.2167.

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Abstract Somatic hypermutation is the most critical mechanism underlying the diversification of Ig genes. Although mutation occurs specifically in B cells during the germinal center reaction, it remains a matter of debate whether the mutation machinery also targets non-Ig genes. We have studied mutations in the 5′ noncoding region of the Bcl6 gene in different subtypes of lymphomas. We found frequent hypermutation in follicular lymphoma (25 of 59 = 42%) (germinal center cell origin) and mucosa-associated lymphoid tissue (MALT) lymphoma (19 of 45 = 42%) (postgerminal center), but only occasionally in mantle cell lymphoma (1 of 21 = 4.8%) (pregerminal center). Most mutations were outside the motifs potentially important for transcription, suggesting they were not important in lymphomagenesis but may, like Ig mutation, represent an inherent feature of the lymphoma precursor cells. Therefore, we investigated their normal cell counterparts microdissected from a reactive tonsil. Bcl6 mutation was found in 13 of 24 (54%) clones from the germinal centre but only in 1 of 24 (4%) clones from the naive B cells of the mantle zone. The frequency, distribution, and nature of these mutations were similar to those resulting from the Ig hypermutation process. The results show unequivocal evidence of non-Ig gene hypermutation in germinal center B cells and provide fresh insights into the process of hypermutation and lymphomagenesis.

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40

Peng, Huai-Zheng, Ming-Qing Du, Athanasios Koulis, Antonella Aiello, Ahmet Dogan, Lang-Xing Pan, and Peter G. Isaacson. "Nonimmunoglobulin Gene Hypermutation in Germinal Center B Cells." Blood 93, no. 7 (April 1, 1999): 2167–72. http://dx.doi.org/10.1182/blood.v93.7.2167.407a35_2167_2172.

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Somatic hypermutation is the most critical mechanism underlying the diversification of Ig genes. Although mutation occurs specifically in B cells during the germinal center reaction, it remains a matter of debate whether the mutation machinery also targets non-Ig genes. We have studied mutations in the 5′ noncoding region of the Bcl6 gene in different subtypes of lymphomas. We found frequent hypermutation in follicular lymphoma (25 of 59 = 42%) (germinal center cell origin) and mucosa-associated lymphoid tissue (MALT) lymphoma (19 of 45 = 42%) (postgerminal center), but only occasionally in mantle cell lymphoma (1 of 21 = 4.8%) (pregerminal center). Most mutations were outside the motifs potentially important for transcription, suggesting they were not important in lymphomagenesis but may, like Ig mutation, represent an inherent feature of the lymphoma precursor cells. Therefore, we investigated their normal cell counterparts microdissected from a reactive tonsil. Bcl6 mutation was found in 13 of 24 (54%) clones from the germinal centre but only in 1 of 24 (4%) clones from the naive B cells of the mantle zone. The frequency, distribution, and nature of these mutations were similar to those resulting from the Ig hypermutation process. The results show unequivocal evidence of non-Ig gene hypermutation in germinal center B cells and provide fresh insights into the process of hypermutation and lymphomagenesis.

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41

Butch, Anthony W., and Moon H. Nahm. "Functional properties of human germinal center B cells." Cellular Immunology 140, no. 2 (April 1992): 331–44. http://dx.doi.org/10.1016/0008-8749(92)90200-9.

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42

Beer, Rebecca L., Michael J. Parsons, and Meritxell Rovira. "Centroacinar cells: At the center of pancreas regeneration." Developmental Biology 413, no. 1 (May 2016): 8–15. http://dx.doi.org/10.1016/j.ydbio.2016.02.027.

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43

Jiang, Shuai. "Dietary Fat Makes Germinal Center B Cells Happy." Cell Metabolism 31, no. 5 (May 2020): 890–91. http://dx.doi.org/10.1016/j.cmet.2020.04.010.

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44

Kroemer, Guido, and Laurence Zitvogel. "CD4+ T Cells at the Center of Inflammaging." Cell Metabolism 32, no. 1 (July 2020): 4–5. http://dx.doi.org/10.1016/j.cmet.2020.04.016.

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45

Vonikakis, V., I. Andreadis, and N. Papamarkos. "Robust document binarization with OFF center-surround cells." Pattern Analysis and Applications 14, no. 3 (April 12, 2011): 219–34. http://dx.doi.org/10.1007/s10044-011-0214-1.

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46

Cyster, Jason G. "Shining a Light on Germinal Center B Cells." Cell 143, no. 4 (November 2010): 503–5. http://dx.doi.org/10.1016/j.cell.2010.10.036.

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47

Monfalcone, Alan P., Marie H. Kosco, Andras K. Szakal, and John G. Tew. "Germinal Center B Cells and Mixed Leukocyte Reactions." Journal of Leukocyte Biology 46, no. 3 (September 1989): 181–88. http://dx.doi.org/10.1002/jlb.46.3.181.

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48

Basso, Katia, Ulf Klein, Huifeng Niu, Gustavo A. Stolovitzky, Yuhai Tu, Andrea Califano, Giorgio Cattoretti, and Riccardo Dalla-Favera. "Tracking CD40 signaling during germinal center development." Blood 104, no. 13 (December 15, 2004): 4088–96. http://dx.doi.org/10.1182/blood-2003-12-4291.

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Abstract Substantial evidence indicates that signaling through the CD40 receptor (CD40) is required for germinal center (GC) and memory B-cell formation. However, it is not fully understood at which stages of B-cell development the CD40 pathway is activated in vivo. To address this question, we induced CD40 signaling in human transformed GC B cells in vitro and identified a CD40 gene expression signature by DNA microarray analysis. This signature was then investigated in the gene expression profiles of normal B cells and found in pre- and post-GC B cells (naive and memory) but, surprisingly, not in GC B cells. This finding was validated in lymphoid tissues by showing that the nuclear factor-κB (NF-κB) transcription factors, which translocate to the nucleus upon CD40 stimulation, are retained in the cytoplasm in most GC B cells, indicating the absence of CD40 signaling. Nevertheless, a subset of centrocytes and B cells in the subepithelium showed nuclear staining of multiple NF-κB subunits, suggesting that a fraction of naive and memory B cells may be subject to CD40 signaling or to other signals that activate NF-κB. Together, these results show that GC expansion occurs in the absence of CD40 signaling, which may act only in the initial and final stages of the GC reaction. (Blood. 2004;104: 4088-4096)

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49

Moser, Emily K. "The Ubiquitin Ligase Itch Regulates Germinal Center Selection." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 96.13. http://dx.doi.org/10.4049/jimmunol.206.supp.96.13.

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Abstract More than 23 million Americans suffer from autoimmune diseases driven by somatically mutated autoantibodies. High levels of somatic hypermutation of immunoglobulin genes occurs in germinal center (GC) B cells. Some of these mutations render autoreactivity, but cells bearing autoreactive receptors are eliminated due to strict selection of GC B cells by mechanisms that are still poorly defined. Inappropriate positive selection signals can rescue autoreactive cells from elimination and drive autoimmune disease. The E3 ubiquitin ligase Itch prevents the emergence of autoimmune disease and autoantibodies in humans and mice, and patients lacking Itch develop debilitating, multi-faceted, potentially fatal, autoimmune disease; yet how Itch regulates GC B cell fate or function is not well understood. By studying Itch deficient mice, we have recently shown that Itch directly limits B cell activity to shape antibody responses. While Itch-deficient mice displayed normal numbers of pre-immune B cell populations, they showed elevated numbers of GC B cells. Mixed bone marrow chimeras revealed that Itch acts within B cells to skew the proportions of light zone and dark zone GC B cells. Proteomic profiling of GC B cells uncovered that Itch deficient cells exhibit hallmarks of positive selection. These results support a novel role for Itch in limiting positive selection of GC B cells to restrict GC size. In this role, Itch may shape the GC-derived antibody repertoire to prevent autoimmunity.

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50

Cohen, E., and P. Sterling. "Microcircuitry related to the receptive field center of the on-beta ganglion cell." Journal of Neurophysiology 65, no. 2 (February 1, 1991): 352–59. http://dx.doi.org/10.1152/jn.1991.65.2.352.

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1. We have investigated the anatomic basis for the Gaussian-like receptive field center of the on-beta ("X") ganglion cell in the area centralis of cat retina. Three adjacent on-beta cells were reconstructed from electron micrographs of 279 serial sections cut vertically through a patch of retina at approximately 1 degree eccentricity. 2. All the bipolar synapses on these cells were identified, and about one-half of these were traced to type b1 bipolar cells, which formed a regular array in the plane of the retina. 3. On average, seven b1 cells contributed to a beta cell: bipolar axons near the middle of the beta dendritic field tended to give many contacts (12-33 contacts); axons near the edge of the field tended to give few contacts (3-4 contacts). 4. Each b1 cell collected from four to seven cones, and the mean number of cones converging through the b1 array to a beta cell was 30. 5. Assuming equal effectiveness for all b1----beta cell synapses, a spatial weighting function was derived from these results. The mean radius of this function at 1/e amplitude for three beta cells was 18.0 +/- 1.1 (SD) microns. This is considerably narrower than the corresponding measurements of the beta cell receptive field center (28 +/- 3 microns) at this eccentricity. 6. It is concluded, in agreement with previous work, that all cones encompassed by the beta cell's dendritic field and those slightly beyond it connect directly to the beta cell via the b1 bipolar cell array. However, the center of the beta cell receptive field is still broader by approximately 60%. This suggests that pooling of cone signals may occur at the level of the outer plexiform layer.

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