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Regulation of germinal center B cell differentiation. Role of the human APO-1/Fas (CD95) molecule

Item Type:Article
Title:Regulation of germinal center B cell differentiation. Role of the human APO-1/Fas (CD95) molecule
Creators Name:Lagresle, C. and Bella, C. and Daniel, P.T. and Krammer, P.H. and Defrance, T.
Abstract:We previously described the existence of a tonsillar IgD- B cell subset with memory B cell features. To test the possibility that these cells could derive from germinal center (GC) B cell precursors, we examined the proliferation, differentiation, and phenotype of GC B cells after culturing with either anti-CD40 Abs or activated T cells, presumably mimicking the signals received by centrocytes in the light zone of GC. We show in this work that GC B cells proliferate and secrete Igs in both activation systems, thus indicating that CD40 ligation is also required for differentiation of GC B cells along the plasmacytoid pathway. T cell-dependent activation of GC B cells induced down-regulation of most GC-related markers (CD10, CD38, and CD77) and up-regulation of CD44 and CD62-L which are both expressed on the putative memory B cells subset. Moreover, T cell-mediated stimulation of GC B cells resulted in the strong induction of CD5 and up-regulation of APO-1/Fas (CD95). In contrast, stimulation performed with immobilized anti-CD40 Abs did not affect expression of CD10 and CD38 and failed to induce CD62-L and CD5, suggesting that the CD40 signaling pathway is necessary but not sufficient for the development of memory B cells. CD95 ligation on GC B cells was found to antagonize the stimulatory effect of immobilized anti-CD40 Abs on their proliferation, survival, and Bcl-2 expression. The possible role of CD95 in the expansion and selection of the Ag-activated B cell clones in GC is discussed.
Keywords:Apoptosis, B-Lymphocyte Differentiation Antigens, B-Lymphocytes, Carrier Proteins, CD Antigens, CD40 Antigens, CD44 Antigens, CD95 Antigens, Cell Adhesion Molecules, Cell Surface Receptors, Down-Regulation, Flow Cytometry, Genetic Techniques, L-Selectin, Lymphocyte Activation, Lymphocyte Homing Receptors, Monoclonal Antibodies, Palatine Tonsil, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Surface Antigens, T-Lymphocytes
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:5746-5756
Date:1 June 1995
Official Publication:http://www.jimmunol.org/cgi/content/abstract/154/11/5746
PubMed:View item in PubMed

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