Regulation of germinal center B cell differentiation. Role of the human APO-1/Fas (CD95) molecule.
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.
Lagresle
C
C
INSERM Unit 404, Institut Pasteur de Lyon, France.
Bella
C
C
Daniel
P T
PT
Krammer
P H
PH
Defrance
T
T
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000954:Antigens, Surface / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens; D002352:Carrier Proteins / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D015536:Down-Regulation / Q000502:physiology; D005434:Flow Cytometry; D005821:Genetic Techniques; D006801:Humans; D018960:Hyaluronan Receptors; D019041:L-Selectin; D008213:Lymphocyte Activation / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D019013:CD40 Antigens; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D019014:fas Receptor; D019041:L-Selectin