Fas-mediated apoptosis eliminates B cells that acquire self-reactivity during the germinal center response to NP.
C57Bl/6 mice with the lpr mutation of Fas (CD95) were tested for deviation from the genetically restricted antibody response to the hapten 4-hydroxy-3-nitrophenyl acetyl (NP). lambda1+ germinal centers (GC) with the canonical v186.2 V(H) gene element develop in lpr/lpr mice with the same time course as in wild-type (+/+) mice. In contrast to +/+ mice, however, lambda1+ GC persist in the spleens of lpr/lpr mice 25 days after immunization. Virtually all of the lambda1+ GC are reactive with NP 10 days after immunization. Sixteen days after immunization, however, many of the lambda1+ GC are not reactive with NP, and few of the lambda1+ GC are reactive with NP 25 days after immunization. The V(H) gene elements of three lambda1+NP- GC 25 days after immunization are derived by somatic mutation of v186.2, but have lost reactivity with NP. The mutated VDJs from these GC react with cells in spleen sections from +/+ and lpr/lpr mice, indicating that they represented secondary antibody responses induced by self antigens that are available as presented antigen. These data indicate that Fas-mediated apoptosis serves to eliminate a (limited) population of B cells that acquire reactivity to "self antigens" by somatic mutation of VDJs in the GC.
Hoch
S
S
Department of Medicine, MCP-Hahnemann University, Philadelphia, Pennsylvania 19107, USA.
Boyd
M
M
Malone
B
B
Gonye
G
G
Schwaber
J
J
Schwaber
J
J
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D018076:DNA, Complementary; D018858:Germinal Center / Q000276:immunology*; D006241:Haptens / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000276:immunology*; D010648:Phenylacetates; D019014:fas Receptor / Q000276:immunology*
D018076:DNA, Complementary; D006241:Haptens; D009596:Nitrophenols; D010648:Phenylacetates; D019014:fas Receptor; C026242:4-hydroxy-5-nitrophenyl acetic acid