Reduced susceptibility to Fas-mediated apoptosis in B-1 cells.
Elimination of activated T and B cells by Fas-dependent apoptosis may contribute to the maintenance of peripheral tolerance. CD40 ligation was recently shown to up-regulate Fas expression and enhance susceptibility to Fas-mediated apoptosis in mouse splenic B cells. In the present study, we have investigated the regulation of Fas expression and Fas-triggered apoptotis in mouse peritoneal B-1 cells. B-1 cells expressed a similar level of CD40 as that on B-2 cells, and proliferated in response to a soluble CD40 ligand (CD40L)-CD8alpha chimeric protein, suggesting that CD40 on B-1 cells is functional. In contrast to B-2 cells, B-1 cells expressed Fas at only low levels in response to CD40L-CD8alpha alone or CD40L-CD8alpha + interleukin-4, and were resistant to Fas-mediated apoptosis following these treatments. While Fas expression could be induced in B-1 cells to a comparable level as that in B-2 cells by cross-linking CD40L-CD8alpha with an anti-CD8alpha antibody, the sensitivity to Fas-mediated apoptosis in B-1 cells was significantly reduced compared with B2 cells. These results suggest that peritoneal B-1 cells from normal mice have a lower susceptibility to Fas-mediated apoptosis and may distinguish B-1 from B-2 cells. Similarly, B-1 cells from the peritoneal cavity and spleen of autoimmune-prone NZB mice exhibited reduced susceptibility to Fas-mediated apoptosis relative to their B-2 counterparts. NZB splenic B-1 cells, however, were more susceptible to Fas-mediated apoptosis than NZB peritoneal B-1 cells. The results presented here raise the possibility that the reduced susceptibility to Fas-triggered apoptosis in B-1 cells might be an accelerating factor for the autoantibody production in NZB mice.
Masuda
K
K
First Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Wang
J
J
Watanabe
T
T
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis / Q000633:toxicity; D023201:CD40 Ligand; D016827:CD8 Antigens / Q000633:toxicity; D002478:Cells, Cultured; D005260:Female; D008024:Ligands; D008562:Membrane Glycoproteins / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010529:Peritoneal Cavity / Q000166:cytology; D013154:Spleen / Q000166:cytology; D019014:fas Receptor / Q000096:biosynthesis / Q000633:toxicity*
D019013:CD40 Antigens; D016827:CD8 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D023201:CD40 Ligand