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1

Mc Dermott, Ray, Umit Ziylan, Danièle Spehner, Huguette Bausinger, Dan Lipsker, Mieke Mommaas, Jean-Pierre Cazenave et al. « Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates ». Molecular Biology of the Cell 13, no 1 (janvier 2002) : 317–35. http://dx.doi.org/10.1091/mbc.01-06-0300.

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Birbeck granules are unusual rod-shaped structures specific to epidermal Langerhans cells, whose origin and function remain undetermined. We investigated the intracellular location and fate of Langerin, a protein implicated in Birbeck granule biogenesis, in human epidermal Langerhans cells. In the steady state, Langerin is predominantly found in the endosomal recycling compartment and in Birbeck granules. Langerin internalizes by classical receptor-mediated endocytosis and the first Birbeck granules accessible to endocytosed Langerin are those connected to recycling endosomes in the pericentriolar area, where Langerin accumulates. Drug-induced inhibition of endocytosis results in the appearance of abundant open-ended Birbeck granule-like structures appended to the plasma membrane, whereas inhibition of recycling induces Birbeck granules to merge with a tubular endosomal network. In mature Langerhans cells, Langerin traffic is abolished and the loss of internal Langerin is associated with a concomitant depletion of Birbeck granules. Our results demonstrate an exchange of Langerin between early endosomal compartments and the plasma membrane, with dynamic retention in the endosomal recycling compartment. They show that Birbeck granules are not endocytotic structures, rather they are subdomains of the endosomal recycling compartment that form where Langerin accumulates. Finally, our results implicate ADP-ribosylation factor proteins in Langerin trafficking and the exchange between Birbeck granules and other endosomal membranes.
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González, M. A. Martinez, et MaPaz Ortega Serrano. « Birbeck-Like Granule in an Epithelial Cell ». Ultrastructural Pathology 18, no 4 (janvier 1994) : 457–58. http://dx.doi.org/10.3109/01913129409023218.

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Chabrol, Eric, Michel Thépaut, Colette Dezutter-Dambuyant, Corinne Vivès, Julien Marcoux, Richard Kahn, Jenny Valladeau-Guilemond, Patrice Vachette, Dominique Durand et Franck Fieschi. « Alteration of the Langerin Oligomerization State Affects Birbeck Granule Formation ». Biophysical Journal 108, no 3 (février 2015) : 666–77. http://dx.doi.org/10.1016/j.bpj.2014.10.075.

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Guenova, Emmanuella, et Martin Schaller. « Residents’ corner September 2011. CarpeDIEM – Birbeck granule in Langerhans cell histiocytosis ». European Journal of Dermatology 21, no 5 (septembre 2011) : 827. http://dx.doi.org/10.1684/ejd.2011.1540.

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Thépaut, Michel, Jenny Valladeau, Alessandra Nurisso, Richard Kahn, Bertrand Arnou, Corinne Vivès, Sem Saeland et al. « Structural Studies of Langerin and Birbeck Granule : A Macromolecular Organization Model†‡ ». Biochemistry 48, no 12 (31 mars 2009) : 2684–98. http://dx.doi.org/10.1021/bi802151w.

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ASANO, Shoichi, Yuko SONODA et Seichiro SAGAMI. « Birbeck granule-like structure (BgS) observed in lymph nodes of DNCB-sensitive mice. » Nishi Nihon Hifuka 48, no 1 (1986) : 61–69. http://dx.doi.org/10.2336/nishinihonhifu.48.61.

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Bucana, Corazon D., C. Gwyneth Munn, Min Ja Song, Kenneth Dunner et Margaret L. Kripke. « Internalization of Ia Molecules into Birbeck Granule-Like Structures in Murine Dendritic Cells ». Journal of Investigative Dermatology 99, no 4 (octobre 1992) : 365–73. http://dx.doi.org/10.1111/1523-1747.ep12616079.

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Strunk, D., K. Rappersberger, C. Egger, H. Strobl, E. Kromer, A. Elbe, D. Maurer et G. Stingl. « Generation of human dendritic cells/Langerhans cells from circulating CD34+ hematopoietic progenitor cells ». Blood 87, no 4 (15 février 1996) : 1292–302. http://dx.doi.org/10.1182/blood.v87.4.1292.bloodjournal8741292.

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Human Langerhans cells (LC) are CD1a+ dendritic cells (DC) that function as potent antigen-presenting cells for primary and secondary immune responses. Limitations in DC/LC numbers, imposed by difficult and tedious isolation procedures, have so far precluded their use as immunogens in the generation and/or augmentation of host responses against various pathogens. Therefore, we have developed a procedure for the generation of human DC/LC from CD34+ hematopoietic progenitor cells (HPC) isolated (mean: 0.7 x 10(6)/ buffy coat and 2.6 x 10(6)/leukapheresis product) and purified ( > 95%) from the peripheral blood of healthy adults. In vitro stimulation of these cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha led to their vigorous proliferation and differentiation resulting in the emergence of CD45+/CD68+/CD3-/CD19- /CD56- leukocytes some of which (mean: 12%) express CD1a and exhibit anti-CD4 and anti-major histocompatibility complex (MHC) class II reactivity. These CD1a- leukocytes include (1) LC as evidenced by the presence of Birbeck granules (BG), (2) CD14+ monocytes, and (3) Birbeck granule-negative cells with a dendritic morphology. Addition of interleukin (IL)-4 to the cytokine cocktail interfered with the development of monocytes and led to a reduction in the overall yield but, on the other hand, resulted in an increased percentage of CD1a+ cells (mean: 24%) among all cells generated. In vitro generated CD1a+, but not CD1a- HPC-derived cells are potent stimulators of the primary mixed leukocyte reaction and, as such, promising candidates for vaccination purposes.
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Strunk, Dirk, Claudia Egger, Gerda Leitner, Daniel Hanau et Georg Stingl. « A Skin Homing Molecule Defines the Langerhans Cell Progenitor in Human Peripheral Blood ». Journal of Experimental Medicine 185, no 6 (17 mars 1997) : 1131–36. http://dx.doi.org/10.1084/jem.185.6.1131.

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We have recently described a system for the generation of dendritic cells (DC) and Langerhans cells (LC) from defined CD34+ precursors purified from peripheral blood of healthy adult volunteers (1). This study has now been extended by the characterization of two distinct subpopulations of CD34+ cells in normal human peripheral blood as defined by the expression of the skin homing receptor cutaneous lymphocyte-associated antigen (CLA). CD34+/CLA+ cells from normal peripheral blood were found to be CD71LOW/CD11a+/CD11b+/CD49d+/ CD45RA+ whereas CD34+/CLA− cells displayed the CD71+/CD11aLOW/CD11bLOW/CD49d(+)/ CD45RALOW phenotype. To determine the differentiation pathways of these two cell populations, CD34+ cells were sorted into CLA+ and CLA− fractions, stimulated with GM-CSF and TNF-α in vitro, and then were cultured for 10 to 18 d. Similar to unfractionated CD34+ cells, the progeny of both cell populations contained sizable numbers (12–22%) of dendritically shaped, CD1a+/HLA-DR+++ cells. In addition to differences in their motility, the two dendritic cell populations generated differed from each other by the expression of LC-specific structures. Only the precursors expressing the skin homing receptor were found to differentiate into LC as evidenced by the presence of Birbeck granules. In contrast, CLA− precursor cells generated a CD1a+ DC population devoid of Birbeck granule–containing LC. Provided that comparable mechanisms as found in this study are also operative in vivo, we postulate that the topographic organization of the DC system is already determined, at least in part, at the progenitor level.
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Strobl, H., E. Riedl, C. Scheinecker, C. Bello-Fernandez, W. F. Pickl, K. Rappersberger, O. Majdic et W. Knapp. « TGF-beta 1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. » Journal of Immunology 157, no 4 (15 août 1996) : 1499–507. http://dx.doi.org/10.4049/jimmunol.157.4.1499.

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Abstract Several studies have demonstrated that dendritic cells (DC) can be generated in vitro from CD34+ hemopoietic progenitor cells. The growth requirements for these cells are poorly characterized, however. In particular, undefined serum/plasma components seem to significantly contribute to in vitro DC development. We report here that the cytokine combination granulocyte-macrophage CSF (GM-CSF) plus TNF-alpha and stem cell factor (SCF) commonly used for the in vitro generation of DC in serum/plasma-supplemented medium is, in the absence of serum supplementation, very inefficient in inducing DC development. We further demonstrate that supplementation with TGF-beta 1 is required for substantial DC development to occur in the absence of serum. Culture of CD34+ cells under serum-free conditions with TGF-beta 1 plus GM-CSF, TNF-alpha, and SCF strongly induces DC differentiation. This culture condition is even more efficient than culturing CD34+ cells with GM-CSF plus TNF-alpha and SCF in the presence of cord blood plasma. The proportions and total yields of cells with typical DC morphology and CD1a molecule expression are higher. The allostimulatory capacity of DC from TGF-beta 1-supplemented, cultures exceeds allostimulation by cells grown in plasma-containing medium. Substantial numbers (21 +/- 7%) of cells grown in TGF-beta 1-supplemented, but not plasma-supplemented, cultures express the Birbeck granule marker molecule Lag and display numerous Birbeck granules. Cells with distinct monocytic features are less frequently observed in TGF-beta 1-supplemented serum-free cultures. The addition of neutralizing anti-TGF-beta 1 Ab abrogates the observed TGF-beta 1 effects.
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Bobryshev, Yuri V., Tsuyoshi Ikezawa et Teruo Watanabe. « Formation of Birbeck granule-like structures in vascular dendritic cells in human atherosclerotic aorta ». Atherosclerosis 133, no 2 (septembre 1997) : 193–202. http://dx.doi.org/10.1016/s0021-9150(97)00129-9.

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Hanau, Daniel, Michel Fabre, Didier Albert Schmitt, Jean-Claude Garaud, Gilles Pauly et Jean-Pierre Cazenave. « Appearance of Birbeck Granule-like Structures in Anti-T6 Antibody-Treated Human Epidermal Langerhans Cells ». Journal of Investigative Dermatology 90, no 3 (mars 1988) : 298–304. http://dx.doi.org/10.1111/1523-1747.ep12456083.

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McDermott, Ray, Huguette Bausinger, Dominique Fricker, Danièle Spehner, Fabienne Proamer, Dan Lipsker, Jean-Pierre Cazenave et al. « Reproduction of Langerin/CD207 Traffic and Birbeck Granule Formation in a Human Cell Line Model ». Journal of Investigative Dermatology 123, no 1 (juillet 2004) : 72–77. http://dx.doi.org/10.1111/j.0022-202x.2004.22728.x.

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Lenormand, Cédric, Coralie Spiegelhalter, Bertrand Cinquin, Sabine Bardin, Huguette Bausinger, Catherine Angénieux, Anita Eckly et al. « Birbeck Granule-Like “Organized Smooth Endoplasmic Reticulum” Resulting from the Expression of a Cytoplasmic YFP-Tagged Langerin ». PLoS ONE 8, no 4 (5 avril 2013) : e60813. http://dx.doi.org/10.1371/journal.pone.0060813.

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Bucana, Corazon D., Gwynneth Munn, Min Ja Song, Kenneth Dunner et Margaret L. Kripke. « Internalization of gold-labeled IA antigens induces formation of Birbeck granule-like structures in murine Langerhans cells ». Proceedings, annual meeting, Electron Microscopy Society of America 48, no 3 (12 août 1990) : 360–61. http://dx.doi.org/10.1017/s0424820100159345.

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Langerhans cells (LC) are migratory bone marrow-derived dendritic cells that reside in the basal portion of the epidermis. LC are antigen presenting cells; they express MHC Class II antigens, macrophage maturation marker, F4/80, and exhibit a distinctive cytoplasmic pentalaminar organelle called Birbeck granules (BG). Murine LC have fewer BG than human LC. The origin of BG is not clear although several reports suggest that BG are formed by invagination of the cytomembrane to form a membrane sandwich.In this study, dendritic cells (DC) from the draining lymph nodes (DLN) of mice previously sensitized with fluorescein isothiocyanate were examined by fluorescence and electron microscopy. Expression of la antigen by dendritic cells was determined by immunogold labeling using either Janssen Auroprobe GAM40 (Amersham Corporation, IL) as the secondary antibody or Protein- A-gold (20nm) (Polysciences, Inc., PA) label. Cells were labeled at 4°C and then warmed to ambient temperature. Samples were taken a t various time intervals and processed for TEM. Serial sections of dendritic cells were examined for presence of BG.
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Kohn, Sarah, et Rachel Friedman-Birnbaum. « Rod-shaped Bodies Resembling Birbeck Granule-like Structures in Endothelial Cells of Dermal Capillaries in Generalized Granuloma Annulare ». Journal of Dermatology 28, no 1 (janvier 2001) : 5–11. http://dx.doi.org/10.1111/j.1346-8138.2001.tb00078.x.

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Gachet, Christian, Daniel Hanau, Danièle Spehner, Christine Brisson, Philippe Ohlmann, Didier A. Schmitt et Jean-Pierre Cazenave. « αIIBβ3 Integrin Dissociation Induced by EDTA Results in Formation of Birbeck Granule-Like Structures in Human Blood Platelets ». Journal of Investigative Dermatology 99, no 5 (novembre 1992) : S27—S29. http://dx.doi.org/10.1111/1523-1747.ep12668284.

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Kissenpfennig, Adrien, Smina Aït-Yahia, Valérie Clair-Moninot, Hella Stössel, Edgar Badell, Yann Bordat, Joanne L. Pooley et al. « Disruption of the langerin/CD207 Gene Abolishes Birbeck Granules without a Marked Loss of Langerhans Cell Function ». Molecular and Cellular Biology 25, no 1 (1 janvier 2005) : 88–99. http://dx.doi.org/10.1128/mcb.25.1.88-99.2005.

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ABSTRACT Langerin is a C-type lectin expressed by a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin is a cell surface receptor that induces the formation of an LC-specific organelle, the Birbeck granule (BG). We generated a langerin − / − mouse on a C57BL/6 background which did not display any macroscopic aberrant development. In the absence of langerin, LC were detected in normal numbers in the epidermis but the cells lacked BG. LC of langerin − / − mice did not present other phenotypic alterations compared to wild-type littermates. Functionally, the langerin − / − LC were able to capture antigen, to migrate towards skin draining lymph nodes, and to undergo phenotypic maturation. In addition, langerin − / − mice were not impaired in their capacity to process native OVA protein for I-A b -restricted presentation to CD4+ T lymphocytes or for H-2K b -restricted cross-presentation to CD8+ T lymphocytes. langerin − / − mice inoculated with mannosylated or skin-tropic microorganisms did not display an altered pathogen susceptibility. Finally, chemical mutagenesis resulted in a similar rate of skin tumor development in langerin − / − and wild-type mice. Overall, our data indicate that langerin and BG are dispensable for a number of LC functions. The langerin − / − C57BL/6 mouse should be a valuable model for further functional exploration of langerin and the role of BG.
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Mackensen, A., B. Herbst, G. Kohler, G. Wolff-Vorbeck, FM Rosenthal, H. Veelken, P. Kulmburg, HE Schaefer, R. Mertelsmann et A. Lindemann. « Delineation of the dendritic cell lineage by generating large numbers of Birbeck granule-positive Langerhans cells from human peripheral blood progenitor cells in vitro ». Blood 86, no 7 (1 octobre 1995) : 2699–707. http://dx.doi.org/10.1182/blood.v86.7.2699.2699.

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Abstract It is well established by in vivo and in vitro studies that dendritic cells (DCs) originate from hematopoietic progenitor cells. However, the presumed intermediate of Birbeck granule (BG)+ Langerhans cells (LCs) has not been detected in cultures derived from bone marrow or peripheral blood progenitor cells (PBPCs), thus contrasting with the data obtained with cord blood. We show here that large numbers of BG+ LCs can be generated from human CD34+ PBPCs in vitro, when granulocyte-macrophage colony-stimulating factor and interleukin-4, potent promotors of LC/DC differentiation, are combined with a cocktail of early acting hematopoietic growth factors. LCs were found to emerge from CD33+CD11b+CD14-progenitor cells that they share with the monocytic lineage. During culture, these cells exhibited a sequence of dramatic morphologic changes, starting with a major increase in granularity followed by an increase in size herein exceeding that of all peripheral blood cells. At the same time, CD1a and major histocompatibility complex class II expression were upregulated and virtually all CD1a++ cells were BG+ by electron microscopy. With prolonged culture, CD1a was downregulated on a major population of cells, paralleled by a loss of BG and an increase of CD4, CD25, and CD80 expression that may correspond to the maturation of epidermal LC in vitro. However, these cells were consistently CD5- and did not exhibit changes in the CD45-isoform expression during culture. The availability of large numbers of these highly purified BG+ LCs and mature DCs allows for specific analysis of these subpopulations and provides a source of potent antigen-presenting cells from individual patients for vaccination protocols against infectious or tumor-associated antigens.
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Mackensen, A., B. Herbst, G. Kohler, G. Wolff-Vorbeck, FM Rosenthal, H. Veelken, P. Kulmburg, HE Schaefer, R. Mertelsmann et A. Lindemann. « Delineation of the dendritic cell lineage by generating large numbers of Birbeck granule-positive Langerhans cells from human peripheral blood progenitor cells in vitro ». Blood 86, no 7 (1 octobre 1995) : 2699–707. http://dx.doi.org/10.1182/blood.v86.7.2699.bloodjournal8672699.

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It is well established by in vivo and in vitro studies that dendritic cells (DCs) originate from hematopoietic progenitor cells. However, the presumed intermediate of Birbeck granule (BG)+ Langerhans cells (LCs) has not been detected in cultures derived from bone marrow or peripheral blood progenitor cells (PBPCs), thus contrasting with the data obtained with cord blood. We show here that large numbers of BG+ LCs can be generated from human CD34+ PBPCs in vitro, when granulocyte-macrophage colony-stimulating factor and interleukin-4, potent promotors of LC/DC differentiation, are combined with a cocktail of early acting hematopoietic growth factors. LCs were found to emerge from CD33+CD11b+CD14-progenitor cells that they share with the monocytic lineage. During culture, these cells exhibited a sequence of dramatic morphologic changes, starting with a major increase in granularity followed by an increase in size herein exceeding that of all peripheral blood cells. At the same time, CD1a and major histocompatibility complex class II expression were upregulated and virtually all CD1a++ cells were BG+ by electron microscopy. With prolonged culture, CD1a was downregulated on a major population of cells, paralleled by a loss of BG and an increase of CD4, CD25, and CD80 expression that may correspond to the maturation of epidermal LC in vitro. However, these cells were consistently CD5- and did not exhibit changes in the CD45-isoform expression during culture. The availability of large numbers of these highly purified BG+ LCs and mature DCs allows for specific analysis of these subpopulations and provides a source of potent antigen-presenting cells from individual patients for vaccination protocols against infectious or tumor-associated antigens.
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McLellan, Alexander D., Michaela Kapp, Andreas Eggert, Christian Linden, Ursula Bommhardt, Eva-B. Bröcker, Ulrike Kämmerer et Eckhart Kämpgen. « Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression ». Blood 99, no 6 (15 mars 2002) : 2084–93. http://dx.doi.org/10.1182/blood.v99.6.2084.

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Abstract Mouse spleen contains CD4+, CD8α+, and CD4−/CD8α− dendritic cells (DCs) in a 2:1:1 ratio. An analysis of 70 surface and cytoplasmic antigens revealed several differences in antigen expression between the 3 subsets. Notably, the Birbeck granule–associated Langerin antigen, as well as CD103 (the mouse homologue of the rat DC marker OX62), were specifically expressed by the CD8α+ DC subset. All DC types were apparent in the T-cell areas as well as in the splenic marginal zones and showed similar migratory capacity in collagen lattices. The 3 DC subtypes stimulated allogeneic CD4+ T cells comparably. However, CD8α+ DCs were very weak stimulators of resting or activated allogeneic CD8+ T cells, even at high stimulator-to-responder ratios, although this defect could be overcome under optimal DC/T cell ratios and peptide concentrations using CD8+ F5 T-cell receptor (TCR)–transgenic T cells. CD8α− or CD8α+DCs presented alloantigens with the same efficiency for lysis by cytotoxic T lymphocytes (CTLs), and their turnover rate of class I–peptide complexes was similar, thus neither an inability to present, nor rapid loss of antigenic complexes from CD8α DCs was responsible for the low allostimulatory capacity of CD8α+ DCs in vitro. Surprisingly, both CD8α+ DCs and CD4−/CD8− DCs efficiently primed minor histocompatibility (H-Y male antigen) cytotoxicity following intravenous injection, whereas CD4+ DCs were weak inducers of CTLs. Thus, the inability of CD8α+ DCs to stimulate CD8+ T cells is limited to certain in vitro assays that must lack certain enhancing signals present during in vivo interaction between CD8α+ DCs and CD8+ T cells.
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Herbst, B., G. Kohler, A. Mackensen, H. Veelken, P. Kulmburg, FM Rosenthal, HE Schaefer, R. Mertelsmann, P. Fisch et A. Lindemann. « In vitro differentiation of CD34+ hematopoietic progenitor cells toward distinct dendritic cell subsets of the birbeck granule and MIIC- positive Langerhans cell and the interdigitating dendritic cell type ». Blood 88, no 7 (1 octobre 1996) : 2541–48. http://dx.doi.org/10.1182/blood.v88.7.2541.bloodjournal8872541.

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We have demonstrated recently that Birbeck granule-positive Langerhans cells (LC) can be derived from CD34+ peripheral blood progenitor cells in the presence of a seven-cytokine cocktail (CC7–7). Here, we show that the sequential use of early-acting hematopoietic growth factors, stem cell factor, interleukin (IL)-3, and IL-6, followed on day 8 by differentiation in the two-factor combination IL-4 plus granulocytemacrophage colony-stimulating factor (GM-CSF) (CC4GM) is more efficient and allows the cells to be arrested in the LC stage for more than 1 week while continuous maturation occurs in CC7–7. Maturation of LC to interdigitating dendritic cells (DC) could specifically be induced within 60 hours by addition of tumor necrosis factor-alpha (20 ng/mL) or lipopolysaccharide (100 ng/mL). Using LC that had been enriched to greater than 90% CD1a+ cells by an immunoaffinity column, we were able to define clear-cut differences between LC and DC that corroborate data of the respective cells derived from epithelial borders (LC) or from lymph nodes (LN) and spleen (DC). Thus, molecules and functions involved in antigen (AG) uptake and processing were highly expressed in LC, while those involved in AG presentation were at maximum in DC. LC were CD1a+2 DR+2, CD23+, CD36+, CD80-, CD86-, and CD25-, while DC were CD1a+/- DR+3, CD23-, CD36-, CD80+, CD86+2, and CD25+, CD40 and CD32 were moderately expressed and nearly unchanged on maturation, in contrast to monocyte-derived DC. Macropinocytosis of fluorescein isothiocyanate-dextran was dominant in LC, as were multilamellar major histocompatibility complex (MHC) class II compartments (MIICs), which were detected by electron microscopy. The functional dichotomy of these cell types was finally supported by testing the AG-presenting cell function for tetanus toxoid to primed autologous T-cell lines, which was optimal when cells were loaded with AG as LC and subsequently induced to become DC.
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Strobl, Herbert, Concha Bello-Fernandez, Elisabeth Riedl, Winfried F. Pickl, Otto Majdic, Stewart D. Lyman et Walter Knapp. « flt3 Ligand in Cooperation With Transforming Growth Factor-β1 Potentiates In Vitro Development of Langerhans-Type Dendritic Cells and Allows Single-Cell Dendritic Cell Cluster Formation Under Serum-Free Conditions ». Blood 90, no 4 (15 août 1997) : 1425–34. http://dx.doi.org/10.1182/blood.v90.4.1425.

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Abstract Using a recently described serum-free culture system of purified human CD34+ progenitor cells, we show here a critical cooperation of flt3 ligand (FL) with transforming growth factor-β1 (TGF-β1) in the induction of in vitro dendritic cell/Langerhans cell (DC/LC) development. The addition of FL to serum-free cultures of CD34+ cells supplemented with TGF-β1, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α, and stem cell factor strongly increases both percentages (mean, 36% ± 5% v 64% ± 4%; P = .001) and total numbers (4.4- ± 0.8-fold) of CD1a+ dendritic cells. These in vitro-generated CD1a+ cells molecularly closely resemble a particular type of DC known as an epidermal Langerhans cell. Generation of DC under serum-free conditions was found to strictly require supplementation of culture medium with TGF-β1. Upon omission of TGF-β1, percentages of CD1a+ DC decreased (to mean, 10% ± 8%; P = .001) and, in turn, percentages of granulomonocytic cells (CD1a− cells that are lysozyme [LZ+]; myeloperoxidase [MPO+]; CD14+) increased approximately threefold (P < .05). Furthermore, in the absence of TGF-β1, FL consistently promotes generation of LZ+, MPO+, and CD14+ cells, but not of CD1a+ cells. Serum-free single-cell cultures set up under identical TGF-β1– and FL-supplemented culture conditions showed that high percentages of CD34+ cells (mean, 18% ± 2%; n = 4) give rise to day-10 DC colony formation. The majority of cells in these DC-containing colonies expressed the Langerhans cell/Birbeck granule specific marker molecule Lag. Without TGF-β1 supplementation, Lag+ colony formation is minimal and formation of monocyte/macrophage-containing colonies predominates. Total cloning efficiency in the absence and presence of TGF-β1 is virtually identical (mean, 41% ± 6% v 41% ± 4%). Thus, FL has the potential to strongly stimulate DC/LC generation, but has a strict requirement for TGF-β1 to show this costimulatory effect.
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Strobl, Herbert, Concha Bello-Fernandez, Elisabeth Riedl, Winfried F. Pickl, Otto Majdic, Stewart D. Lyman et Walter Knapp. « flt3 Ligand in Cooperation With Transforming Growth Factor-β1 Potentiates In Vitro Development of Langerhans-Type Dendritic Cells and Allows Single-Cell Dendritic Cell Cluster Formation Under Serum-Free Conditions ». Blood 90, no 4 (15 août 1997) : 1425–34. http://dx.doi.org/10.1182/blood.v90.4.1425.1425_1425_1434.

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Using a recently described serum-free culture system of purified human CD34+ progenitor cells, we show here a critical cooperation of flt3 ligand (FL) with transforming growth factor-β1 (TGF-β1) in the induction of in vitro dendritic cell/Langerhans cell (DC/LC) development. The addition of FL to serum-free cultures of CD34+ cells supplemented with TGF-β1, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α, and stem cell factor strongly increases both percentages (mean, 36% ± 5% v 64% ± 4%; P = .001) and total numbers (4.4- ± 0.8-fold) of CD1a+ dendritic cells. These in vitro-generated CD1a+ cells molecularly closely resemble a particular type of DC known as an epidermal Langerhans cell. Generation of DC under serum-free conditions was found to strictly require supplementation of culture medium with TGF-β1. Upon omission of TGF-β1, percentages of CD1a+ DC decreased (to mean, 10% ± 8%; P = .001) and, in turn, percentages of granulomonocytic cells (CD1a− cells that are lysozyme [LZ+]; myeloperoxidase [MPO+]; CD14+) increased approximately threefold (P < .05). Furthermore, in the absence of TGF-β1, FL consistently promotes generation of LZ+, MPO+, and CD14+ cells, but not of CD1a+ cells. Serum-free single-cell cultures set up under identical TGF-β1– and FL-supplemented culture conditions showed that high percentages of CD34+ cells (mean, 18% ± 2%; n = 4) give rise to day-10 DC colony formation. The majority of cells in these DC-containing colonies expressed the Langerhans cell/Birbeck granule specific marker molecule Lag. Without TGF-β1 supplementation, Lag+ colony formation is minimal and formation of monocyte/macrophage-containing colonies predominates. Total cloning efficiency in the absence and presence of TGF-β1 is virtually identical (mean, 41% ± 6% v 41% ± 4%). Thus, FL has the potential to strongly stimulate DC/LC generation, but has a strict requirement for TGF-β1 to show this costimulatory effect.
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Jaksits, Silvia, Ernst Kriehuber, Anne Sophie Charbonnier, Klemens Rappersberger, Georg Stingl et Dieter Maurer. « CD34+ Cell-Derived CD14+ Precursor Cells Develop into Langerhans Cells in a TGF-β1-Dependent Manner ». Journal of Immunology 163, no 9 (1 novembre 1999) : 4869–77. http://dx.doi.org/10.4049/jimmunol.163.9.4869.

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Abstract Langerhans cells (LC) are CD1a+E-cadherin (E-cad)+Birbeck granule+ but CD11b−CD36−factor XIIIa (FXIIIa)− members of the dendritic cell (DC) family. Evidence holds that LC originate from CD1a+CD14− rather than CD14+CD1a− progenitors, both of which arise from GM-CSF/TNF-α-stimulated CD34+ stem cells. The CD14+CD1a− progenitors, on the other hand, can give rise to a separate DC type characterized by its CD1a+CD11b+CD36+FXIIIa+E-cad−BG− phenotype (non-LC DC). Although GM-CSF/TNF-α are important for both LC and non-LC DC differentiation, TGF-β1 is thought to preferentially promote LC development in vitro and in vivo. However, the hemopoietic biology of this process and the nature of TGF-β1-responsive LC precursors (LCp) are not well understood. Here we show that CD14+ precursors in the presence, but not in the absence, of TGF-β1 give rise to a progeny that fulfills all major criteria of LC. In contrast, LC development from CD1a+ progenitors was TGF-β1 independent. Further studies revealed that CD14+ precursors contain a CD11b+ and a CD11b− subpopulation. When either subset was stimulated with GM-CSF/TNF-α and TGF-β1, only CD14+CD11b− cells differentiated into LC. The CD11b+ cells, on the other hand, acquired non-LC DC features only. The higher doubling rates of cells entering the CD14+ LCp rather than the CD1a+ LCp pathway add to the importance of TGF-β1 for LC development. Because CD14+CD11b− precursors are multipotent cells that can enter LC or macrophage differentiation, it is suggested that these cells, if present at the tissue level, endow a given organ with the property to generate diverse cell types in response to the local cytokine milieu.
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Bartosik, J., A. Andersson, S. Axelsson, B. Falck et A. Ringberg. « Direct evidence for the cytomembrane derivation of Birbeck granules : the membrane-sandwich effect ». Acta Dermato-Venereologica 65, no 2 (1 mars 1985) : 157–60. http://dx.doi.org/10.2340/0001555565157160.

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Digitonin, which is known to cause extensive damage to cytomembranes in general, was found to have a most remarkable effect on epidermal Langerhans´ cells. Thus, it generates a membrane-sandwiching process resulting in the formation of large discs which except for the differences in size have the same morphology as ordinary Birbeck granules. This demonstrates that the cytomembrane of the Langerhans´ cell has the inherent ability to superimpose upon itself, leaving little doubt that the normal Birbeck granules derive from the cytomembrane.
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27

Loy, Timothy S. « Intranuclear Birbeck Granules in Langerhans Cell Histiocytosis ». Ultrastructural Pathology 21, no 6 (janvier 1997) : 597–600. http://dx.doi.org/10.3109/01913129709016376.

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Kaplan, G., G. Walsh, L. S. Guido, P. Meyn, R. A. Burkhardt, R. M. Abalos, J. Barker, P. A. Frindt, T. T. Fajardo et R. Celona. « Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor : Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing. » Journal of Experimental Medicine 175, no 6 (1 juin 1992) : 1717–28. http://dx.doi.org/10.1084/jem.175.6.1717.

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Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged.
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Robb, Ian A., Carmencita L. Jimenez et Blair F. Carpenter. « Birbeck Granules or Birbeck Junctions ? Intercellular “Zipperlike” Lattice Junctions in Eosinophilic Granuloma of Bone ». Ultrastructural Pathology 16, no 4 (janvier 1992) : 423–28. http://dx.doi.org/10.3109/01913129209057827.

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Bonetti, Maria Ida, Laura Pieri, Lola Domenici, Serena Urbani, Giovanni Romano, Alessandra Aldinucci, Clara Ballerini et al. « Dendritic cells with lymphocyte-stimulating activity differentiate from human CD133 positive precursors ». Blood 117, no 15 (14 avril 2011) : 3983–95. http://dx.doi.org/10.1182/blood-2010-08-299735.

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Abstract CD133 is a hallmark of primitive myeloid progenitors. We have addressed whether human cord blood cells selected for CD133 can generate dendritic cells, and Langerhans cells in particular, in conditions that promote that generation from CD34+ progenitors. Transforming growth factor-β1 (TGF-β1) and anti–TGF-β1 antibody, respectively, were added in some experiments. With TGF-β, monocytoid cells were recognized after 7 days. Immunophenotypically immature dendritic cells were present at day 14. After 4 more days, the cells expressed CD54, CD80, CD83, and CD86 and were potent stimulators in mixed lymphocyte reaction; part of the cells expressed CD1a and langerin, but not Birbeck granules. Without TGF-β, only a small fraction of cells acquired a dendritic shape and expressed the maturation-related antigens, and lymphocytes were poorly stimulated. With anti–TGF-β, the cell growth was greatly hampered, CD54 and langerin were never expressed, and lymphocytes were stimulated weakly. In conclusion, CD133+ progenitors can give rise in vitro, through definite steps, to mature, immunostimulatory dendritic cells with molecular features of Langerhans cells, although without Birbeck granules. Addition of TGF-β1 helps to stimulate cell growth and promotes the acquisition of mature immunophenotypical and functional features. Neither langerin nor Birbeck granules proved indispensable for lymphocyte stimulation.
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31

Hashimoto, Ken, Hiroshi Fujiwara et Keiko Fujiwara. « Birbeck granules, worm-like bodies and “lupus erythematosus virus” ». European Journal of Dermatology 26, no 5 (septembre 2016) : 444–51. http://dx.doi.org/10.1684/ejd.2016.2840.

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Mommaas, Mieke, A. a. t. Mulder, Bert Jan Vermeer et Frits Koning. « Functional Human Epidermal Langerhans Cells that Lack Birbeck Granules ». Journal of Investigative Dermatology 103, no 6 (décembre 1994) : 807–10. http://dx.doi.org/10.1111/1523-1747.ep12413456.

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Mommaas, AM, AA Mulder, F. Koning et BJ Vermeer. « Functional human epidermal Langerhans cells that lack birbeck granules ». Journal of Dermatological Science 6, no 1 (août 1993) : 48. http://dx.doi.org/10.1016/0923-1811(93)90994-z.

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Lindelöf, B., B. Forslind, M. Hilliges, O. Johansson et L. Aström. « Langerhans' cell histiocytosis in an adult. » Acta Dermato-Venereologica 71, no 2 (1 janvier 1991) : 178–80. http://dx.doi.org/10.2340/0001555571178180.

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A woman with typical skin lesions of histiocytosis X is reported. Electron microscopic and immunohistochemical investigations revealed a large number of markedly long Birbeck Langerhans' cell granulae. During treatment with Interferon alpha -2b, the patient developed infarctus cerebri and died.
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35

Nyfors, A., et PG Krüger. « Langerhans´ cells in seborrheic keratosis. A clinical and ultrastructural study ». Acta Dermato-Venereologica 65, no 4 (1 juillet 1985) : 333–35. http://dx.doi.org/10.2340/0001555565333335.

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Skin biopsies from 10 patients with seborrheic keratoses were examined by electron microscopy for the presence of Langerhans´ cells. Comparing seborrheic keratoses with normal skin of the same patient and with normal skin from controls, neither an increased number of Langerhans´ cells nor an increased number of specific granules, Birbeck granules, nor abnormal Langerhans´ cells, was found. Melanosomes in a Langerhans´ cell were observed in 2 seborrheic keratoses, suggesting phagocytic activity of the Langerhans´ cell.
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36

Byard, R. W., M. Carli et H. Thiele. « How useful are Birbeck granules in the diagnosis of histiocytosis ». Pathology 26, no 1 (1994) : A1. http://dx.doi.org/10.1016/s0031-3025(16)35507-6.

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Vital, Anne, Hugues Loiseau, Guy Kantor, Claude Vital et François Cohadon. « Primary Langerhans' cell histiocytosis of the central nervous system with fatal outcome ». Journal of Neurosurgery 85, no 6 (décembre 1996) : 1156–60. http://dx.doi.org/10.3171/jns.1996.85.6.1156.

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✓ An unusual case of primary parenchymal Langerhans' cell histiocytosis of the central nervous system is reported. The definitive diagnosis was obtained by ultrastructural detection of Birbeck granules and by immunohistochemical evidence of CD1a expression. Despite complete surgical resection, there was an early recurrence with multiple central nervous system metastases leading to a fatal outcome.
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Thornton, Shantae M., Varsha D. Samararatne, Joseph G. Skeate, Christopher Buser, Kim P. Lühen, Julia R. Taylor, Diane M. Da Silva et W. Martin Kast. « The Essential Role of anxA2 in Langerhans Cell Birbeck Granules Formation ». Cells 9, no 4 (15 avril 2020) : 974. http://dx.doi.org/10.3390/cells9040974.

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Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have historically focused on morphological characterizations, but BG have also been implicated in viral antigen processing which suggests that they can serve a function in antiviral immunity. This study focused on investigating proteins that could be involved in BG formation to further characterize their structure using transmission electron microscopy (TEM). Here, we report a critical role for the protein annexin A2 (anxA2) in the proper formation of BG structures. When anxA2 expression is downregulated, langerin expression decreases, cytoplasmic BG are nearly ablated, and the presence of malformed BG-like structures increases. Furthermore, in the absence of anxA2, we found langerin was no longer localized to BG or BG-like structures. Taken together, these results indicate an essential role for anxA2 in facilitating the proper formation of BG.
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39

Valladeau, J., et S. Saeland. « La Langerine et les granules de Birbeck des cellules de Langerhans. » médecine/sciences 16, no 8-9 (2000) : 979. http://dx.doi.org/10.4267/10608/1769.

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PÉREZ-TORRES, ARMANDO, et MARTHA USTARROZ-CANO. « Demonstration of Birbeck (Langerhans cells) granules in the normal chicken epidermis ». Journal of Anatomy 199, no 4 (octobre 2001) : 493–97. http://dx.doi.org/10.1046/j.1469-7580.2001.19940493.x.

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Deng, April, Wendy Lee, Richard Pfau, Allan Harrington, John DiGiovani, Kyle A. Prickett, David M. Dare et John P. Petrali. « Primary cutaneous Langerhans cell sarcoma without Birbeck granules : indeterminate cell sarcoma ? » Journal of Cutaneous Pathology 35, no 9 (septembre 2008) : 849–54. http://dx.doi.org/10.1111/j.1600-0560.2007.00907.x.

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PÉREZ-TORRES, ARMANDO, et MARTHA USTARROZ-CANO. « Demonstration of Birbeck (Langerhans cells) granules in the normal chicken epidermis ». Journal of Anatomy 199, no 4 (octobre 2001) : 493–97. http://dx.doi.org/10.1017/s002187820100855x.

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Chauffaille, Maria de Lourdes L. F., Rosana M. Valério, Cybelle Maria Costa Diniz, Milvia Maria Simões, Silva Enokihara, Nylceo Michalany, Karin Ventura Ferreira et al. « Langerhans cell histiocytosis ». Sao Paulo Medical Journal 116, no 1 (février 1998) : 1625–28. http://dx.doi.org/10.1590/s1516-31801998000100006.

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The authors present a rare case of Langerhans cell histiocytosis in a 31 year old female patient with vulvar, peri-anal and oral lesions, diabetes insipidus, pulmonary skin and bone infiltrations. Skin biopsy immunohistochemistry presented positive S100 protein and vimentine, but the diagnosis was done with the demonstration of Birbeck granules with eletronic mucroscopy. The treatment was based on systemical chemotherapy although vulvar lesion has a bad response to chemotherapy.
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44

Bartosik, J., C. J. Lamm et B. Falck. « Quantification of Birbeck's granules in human Langerhans' cells. » Acta Dermato-Venereologica 71, no 3 (1 janvier 1991) : 209–13. http://dx.doi.org/10.2340/0001555571209213.

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A proper understanding of the function of Birbeck's granules requires that they should be counted under various conditions. We now present a simple quantification method which does not depend on specific assumptions concerning size, shape or location of the particles counted and can, moreover, be applied for counting other subcellular structures as well. A population of 69 serially sectioned human Langerhans' cells had an average of 290 granules and no cell contained fewer than 96 granules, indicating that as they degrade, granules are continuously formed. Suprabasal Langerhans' cells contained significantly more granules than did the basal cells.
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45

Stössel, H., F. Koch, E. Kämpgen, P. Stöger, A. Lenz, C. Heufler, N. Romani et G. Schuler. « Disappearance of certain acidic organelles (endosomes and Langerhans cell granules) accompanies loss of antigen processing capacity upon culture of epidermal Langerhans cells. » Journal of Experimental Medicine 172, no 5 (1 novembre 1990) : 1471–82. http://dx.doi.org/10.1084/jem.172.5.1471.

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Freshly isolated epidermal Langerhans cells (LC) can actively process native protein antigens, but are weak in sensitizing helper T cells. During culture, when LC mature into potent immunostimulatory dendritic cells, T cell sensitizing capacity develops but antigen processing capacity is downregulated. Processing of exogenous antigens for class II-restricted antigen presentation involves acidic organelles. We used the DAMP-technique to monitor acidic organelles at the ultrastructural level in fresh, as well as cultured, mouse and human LC. We observed that the loss of antigen processing capacity with culture of LC was reflected by the disappearance of certain acidic organelles, namely endosomes (particularly early ones), and the hitherto enigmatic LC granules ("Birbeck Granules"). Our findings support the notion that endosomes are critical for antigen processing and suggest that LC granules might be involved as well.
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46

Uzan-Gafsou, Stéphanie, Huguette Bausinger, Fabienne Proamer, Solange Monier, Dan Lipsker, Jean-Pierre Cazenave, Bruno Goud, Henri de la Salle, Daniel Hanau et Jean Salamero. « Rab11A Controls the Biogenesis of Birbeck Granules by Regulating Langerin Recycling and Stability ». Molecular Biology of the Cell 18, no 8 (août 2007) : 3169–79. http://dx.doi.org/10.1091/mbc.e06-09-0779.

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The extent to which Rab GTPases, Rab-interacting proteins, and cargo molecules cooperate in the dynamic organization of membrane architecture remains to be clarified. Langerin, a recycling protein accumulating in the Rab11-positive compartments of Langerhans cells, induces the formation of Birbeck granules (BGs), which are membrane subdomains of the endosomal recycling network. We investigated the role of Rab11A and two members of the Rab11 family of interacting proteins, Rip11 and RCP, in Langerin traffic and the biogenesis of BGs. The overexpression of a dominant-negative Rab11A mutant or Rab11A depletion strongly influenced Langerin traffic and stability and the formation of BGs, whereas modulation of other Rab proteins involved in dynamic regulation of the endocytic-recycling pathway had no effect. Impairment of Rab11A function led to a missorting of Langerin to lysosomal compartments, but inhibition of Langerin degradation by chloroquine did not restore the formation of BGs. Loss of RCP, but not of Rip11, also had a modest, but reproducible effect on Langerin stability and BG biogenesis, pointing to a role for Rab11A–RCP complexes in these events. Our results show that Rab11A and Langerin are required for BG biogenesis, and they illustrate the role played by a Rab GTPase in the formation of a specialized subcompartment within the endocytic-recycling system.
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47

Fujita, M., M. Kashihara-Sawami, Y. Horiguchi, F. Furukawa, M. Ueda et S. Imamura. « Langerhans cells in human allergic contact dermatitis contain varying numbers of birbeck granules ». Histochemistry 94, no 5 (septembre 1990) : 497–504. http://dx.doi.org/10.1007/bf00272613.

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48

Caux, C., B. Vanbervliet, C. Massacrier, C. Dezutter-Dambuyant, B. de Saint-Vis, C. Jacquet, K. Yoneda, S. Imamura, D. Schmitt et J. Banchereau. « CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha. » Journal of Experimental Medicine 184, no 2 (1 août 1996) : 695–706. http://dx.doi.org/10.1084/jem.184.2.695.

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Human dendritic cells (DC) can now be generated in vitro in large numbers by culturing CD34+ hematopoietic progenitors in presence of GM-CSF+TNF alpha for 12 d. The present study demonstrates that cord blood CD34+ HPC indeed differentiate along two independent DC pathways. At early time points (day 5-7) during the culture, two subsets of DC precursors identified by the exclusive expression of CD1a and CD14 emerge independently. Both precursor subsets mature at day 12-14 into DC with typical morphology and phenotype (CD80, CD83, CD86, CD58, high HLA class II). CD1a+ precursors give rise to cells characterized by the expression of Birbeck granules, the Lag antigen and E-cadherin, three markers specifically expressed on Langerhans cells in the epidermis. In contrast, the CD14+ progenitors mature into CD1a+ DC lacking Birbeck granules, E-cadherin, and Lag antigen but expressing CD2, CD9, CD68, and the coagulation factor XIIIa described in dermal dendritic cells. The two mature DC were equally potent in stimulating allogeneic CD45RA+ naive T cells. Interestingly, the CD14+ precursors, but not the CD1a+ precursors, represent bipotent cells that can be induced to differentiate, in response to M-CSF, into macrophage-like cells, lacking accessory function for T cells. Altogether, these results demonstrate that different pathways of DC development exist: the Langerhans cells and the CD14(+)-derived DC related to dermal DC or circulating blood DC. The physiological relevance of these two pathways of DC development is discussed with regard to their potential in vivo counterparts.
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Merai, Hema, David Collas, Ashish Bhagat et Uday Mandalia. « Erdheim-Chester Disease : A Case Report and Review of the Literature ». Journal of Clinical Imaging Science 10 (18 juin 2020) : 37. http://dx.doi.org/10.25259/jcis_68_2020.

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Erdheim-Chester disease (ECD) is a rare form of non-Langerhans’ cell histiocytosis characterized by xanthogranulomatous infiltration of foamy histiocytes surrounded by fibrosis. ECD may be asymptomatic or present as a multi-systemic disease with life-threatening manifestations, most commonly involving the skeletal system. Immunohistochemical staining demonstrates cells that are CD68+, CD1a–, and S100– with an absence of Birbeck granules. We report a case of a 69-year old male patient who presented with neurological symptoms – eventually thought to be separate to his diagnosis of ECD. It represents the ability to diagnose ECD based just on radiological findings in an otherwise asymptomatic individual.
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Kim, Eun-Young, Joong-Uhn Choi, Tai-Seung Kim, Dong-Ik Kim et Kir-Young Kim. « Huge Langerhans cell histiocytosis granuloma of choroid plexus in a child with Hand-Schüller-Christian disease ». Journal of Neurosurgery 83, no 6 (décembre 1995) : 1080–84. http://dx.doi.org/10.3171/jns.1995.83.6.1080.

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✓ In the literature, only two previous cases of presumed Langerhans cell histiocytosis (LCH) granuloma involving choroid plexus have been reported in patients with Hand-Schüller-Christian (HSC) disease, but those cases were not verified by immunohistochemistry or electron microscopy. The authors report a case of LCH granuloma of the choroid plexuses of bilateral lateral ventricles and the fourth ventricle in a child affected by HSC disease. This disease was confirmed by the presence of Birbeck granules on electron microscopy and positive reactivity to S-100 protein. Clinical, radiographic, and histological features are discussed. This case illustrates that LCH granuloma should be considered in the differential diagnosis of intraventricular masses.
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