FAS is highly expressed in the germinal center but is not required for regulation of the B-cell response to antigen.
In establishing the memory B-cell population and maintaining self-tolerance during an immune response, apoptosis mediates the removal of early, low-affinity antibody-forming cells, unselected germinal center (GC) cells, and, potentially, self-reactive B cells. To address the role of the apoptosis-signaling cell surface molecule FAS in the B-cell response to antigen, we have examined the T-cell-dependent B-cell response to the carrier-conjugated hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) in lpr mice in which the fas gene is mutated. High levels of FAS were expressed on normal GC B cells but the absence of FAS did not perturb the progressive decline in numbers of either GC B cells or extrafollicular antibody-forming cells. Furthermore, the rate of formation and eventual size of the NP-specific memory B-cell population in lpr mice were normal. The accumulation of cells with affinity-enhancing mutations and the appearance of high-affinity anti-NP IgG1 antibody in the serum were also normal in lpr mice. Thus, although high levels of FAS are expressed on GC B cells, FAS is not required for GC selection or for regulation of the major antigen-specific B-cell compartments. The results suggest that the size and composition of B-cell compartments in the humoral immune response are regulated by mechanisms that do not require FAS.
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
K G
KG
Smith
G J
GJ
Nossal
D M
DM
Tarlinton
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D000917:Antibody Formation; D000921:Antibody-Producing Cells; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D018858:Germinal Center / Q000737:chemistry*; D006241:Haptens / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D019014:fas Receptor / Q000032:analysis* / Q000235:genetics
D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009596:Nitrophenols; D010648:Phenylacetates; D019014:fas Receptor; C026242:4-hydroxy-5-nitrophenyl acetic acid