Apoptosis induced by the antigen receptor and Fas in a variant of the immature B cell line WEHI-231 and in splenic immature B cells.
Signaling by the BCR causes proliferation and resistance to Fas-induced apoptosis in mature B cells, but growth arrest and apoptosis in immature B cells. We have identified a variant of the immature B cell line WEHI 231 that retains the apoptotic response to the BCR but has acquired susceptibility to Fas-induced apoptosis. The Fas susceptibility was associated with increased Fas expression on the cell surface and down-regulated IgD expression. These cells exhibited a distinctive functional relationship in response to signals from the BCR, Fas and CD40: BCR stimulation markedly promoted Fas-mediated apoptosis (and vice versa) and Fas-induced apoptosis was not subject to modulation by CD40 signaling. While BCR-induced apoptosis was effectively rescued by CD40, it was not affected by the expression of a dominant-negative FADD. The mechanistic distinctions between BCR- and Fas-induced apoptosis were further characterized by the differential effects of different caspase inhibitors on these two processes which imply the involvement of different subsets of caspases. For BCR-induced apoptosis, we provide evidence that the final apoptotic destruction phase can be inhibited by the pan-caspase inhibitor BOC-Asp-FMK (BD) and that, in the presence of BD, the BCR only induces growth arrest which is reversible. The striking enhancing effects of Fas on BCR-induced apoptosis seen in the variant cells prompted us to examine if a similar cooperation in induction of apoptosis occurs in the highly tolerizable immature B cells of the spleen. We found that the splenic immature B population contains a significant number of Fas-expressing cells, but neither Fas-induced apoptosis nor an enhancing effect of Fas on BCR-induced apoptosis of these cells was detected in vitro.
G. W. Hooper Foundation & Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0552, USA.
M T
MT
Tian
C H
CH
Chou
A L
AL
DeFranco
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology* / Q000378:metabolism
D019013:CD40 Antigens; D011947:Receptors, Antigen, B-Cell; D019014:fas Receptor