The lpr gene encodes a defective form of Fas, a cell surface protein that mediates apoptosis. This defect blocks apoptotic deletion of autoreactive T and B cells, leading to lymphoproliferation and lupus-like autoantibody production. The effects of the lpr Fas mutation on other kinds of physiologically relevant apoptosis are largely undocumented. To assess whether some of the apoptosis known to occur after ionizing radiation might be mediated by Fas͞Fas ligand (FasL) interactions, we quantitated in vitro apoptosis by f low cytometry measurement of DNA content in splenic T and B cells from irradiated 5-to 8-month-old B6͞lpr mice. Total apoptosis of both lpr and control cells was substantial after treatment; however there was a significant difference between B6 (73%) and lpr (25%) lymphocyte apoptosis. Thy1, CD4, CD8, and IgM cells from lpr showed much lower levels of apoptosis than control cells after irradiation. Apoptosis induced by heat shock was also impaired in lpr. The finding that ␥-irradiation increased Fas expression on B6 cells and that irradiation-induced apoptosis could be blocked with a Fas-Fc fusion protein further supported the possible involvement of Fas in this form of apoptosis. Fas͞FasL interactions may thus play an important role in identifying and eliminating damaged cells after ␥-irradiation and other forms of injury.

Cross-linking of cell surface Fas (CD95) mediates rapid apoptosis.' The insight that the autoimmune and lymphoproliferative disorder of lpr and gld mice is due to mutations in Fas and Fas ligand (FasL), respectively, has heightened interest in the biological significance of the Fas receptor? Through induction of cell death, Fas controls the extent of T cell receptor-mediated T cell responses in the periphery and mediates a major part of cytotoxic T cell killing.3 Fas-FasL interactions may also limit the clonal expansion of B lymphocyte^.^