Concurrent engagement of CD40 and the antigen receptor protects naive and memory human B cells from APO-1/Fas-mediated apoptosis.
Naive and memory B cells were isolated from human tonsils and examined for expression of APO-1/Fas and for their sensitivity to the APO-1-dependent apoptosis. APO-1 was found to be constitutively expressed on memory but not on naive B cells. The susceptibility of both cell types to the APO-1 apoptotic pathway was acquired upon CD40 triggering and was correlated with increased expression of the APO-1 receptor. Both naive and memory B cells were protected from the APO-1-mediated death signal after dual ligation of the Ag receptor adn CD40. Our findings suggest that the APO-1 pathway controls the specificity of B cell responses to T-dependent Ags and that occupancy of the Ag receptor dictates the outcome of APO-1-ligation on B cell survival.
Lagresle
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C
Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 404, "Immunité et Vaccination," Institut Pasteur de Lyon, France.
Mondière
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P
Bella
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Krammer
P H
PH
Defrance
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T
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007152:Immunologic Capping; D007156:Immunologic Memory; D007378:Interleukins / Q000494:pharmacology; D008213:Lymphocyte Activation; D008459:Measles virus / Q000276:immunology; D018448:Models, Immunological; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism
D015703:Antigens, CD; D019013:CD40 Antigens; D007136:Immunoglobulins; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D019014:fas Receptor