Protection against Fas-dependent Th1-mediated apoptosis by antigen receptor engagement in B cells.
Cytotoxic CD4+ Th1-cells induce cell death by triggering a Fas-dependent apoptotic pathway. Potential targets include activated B cells, but it is not known whether the mode of B-cell stimulation influences susceptibility to Th1-mediated cytotoxicity. Here we report that CD40-ligand-stimulated B cells were extremely sensitive, whereas anti-IgM-stimulated B cells were resistant, to Fas-mediated apoptosis. B cells stimulated by both CD40L and anti-IgM were not susceptible to cytolysis, demonstrating that anti-IgM-mediated protection is an active, dominant process. Resistance to Th1-mediated cytotoxicity was similarly observed in CD40L-stimulated 3-83 (anti-H-2Kk,b) transgenic B cells co-cultured with H-2Kk or H-2Kb (but not H-2Kd) splenocytes. These results indicate that B cells can participate in regulating their own destruction. Protection against Fas-dependent apoptosis afforded by immunoglobulin-receptor engagement may constitute a fail-safe mechanism that eliminates bystander B cells activated by CD40L-expressing T cells, but ensures survival of antigen-specific B cells.
Rothstein
T L
TL
Department of Medicine, Evans Memorial Department of Clinical Research, Boston University Medical Center, Massachusetts 02118.
Wang
J K
JK
Panka
D J
DJ
Foote
L C
LC
Wang
Z
Z
Stanger
B
B
Cui
H
H
Ju
S T
ST
Marshak-Rothstein
A
A
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens; D023201:CD40 Ligand; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D007075:Immunoglobulin M / Q000276:immunology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology*; D019014:fas Receptor
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D019013:CD40 Antigens; D017931:DNA Primers; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D019014:fas Receptor; D023201:CD40 Ligand