CERAMIDE MEDIATES THE APOPTOTIC RESPONSE OF WEHI-231 CELLS TO ANTIIMMUNOGLOBULIN, CORTICOSTEROIDS AND IRRADIATION

We demonstrate for the first time how immature B cells kill themselves . Ceramide is identified as the mediator of apoptosis in the murine B lymphoma line WEHI 231 commonly used as a model to study clonal deleti on in B lymphocytes. We show that exogenous ceramide induces apoptosis in WEHI 231 cells. To maintain self tolerance, immature lymphocytes r eadily undergo apoptotic death in response to the cross-linking of the ir antigen-specific receptors. We demonstrate that endogenously produc ed ceramide accumulates in WEHI 231 cells exposed to anti-IgM, an anti gen surrogate before the onset of apoptosis. We also show that two oth er inducers of apoptosis, irradiation and dexamethasone, cause intrace llular accumulation of ceramide. (C) 1994 Academic Press, Inc.