The in vivo balance between B cell clonal expansion and elimination is regulated by CD95 both on B cells and in their micro-environment.
The expression of CD95 (Fas/APO-1) on B cells has been shown to play a direct role in their fate. B cells that chronically bind antigen due to prolonged antigen exposure, such as self-reactive B cells, are induced to express CD95 by CD40 ligand (CD40L) and are subsequently eliminated by CD95 ligand (CD95L) when they present antigen to CD4+ T cells. B cells that bind antigen acutely due to sudden antigen encounter, such as foreign antigen reactive B cells, up-regulate CD95, but are normally protected from CD95L-mediated apoptosis. Here, however, it is shown in vivo that foreign antigen-specific B cells fail to be protected from CD95-dependent elimination in a host that is CD95 deficient, regardless of antigenic challenge. These data indicate that B cell antigen receptor (BCR)-induced protection against CD95L-mediated apoptosis is not absolute but depends upon other micro-environmental factors in vivo. The normal balance between T cell-dependent humoral immunity and tolerance is thus regulated intrinsically by CD95 expression on responding B cells, and extrinsically by CD95-mediated control of CD95L or other molecules in the lymphoid micro-environment.
Rathmell
J C
JC
Immunology Program, Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University, California, USA.
Goodnow
C C
CC
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D015152:Blotting, Northern; D005434:Flow Cytometry; D007111:Immunity, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D019014:fas Receptor