Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis

Abstract

Activation of the cell surface receptor Fas/APO-1 (CD95) induces apoptosis in lymphocytes and regulates immune responses. The cytoplasmic membrane protein Bcl-2 inhibits lymphocyte killing by diverse cytotoxic agents, but we found it provided little protection against Fas/APO-1-transduced apoptosis in B lymphoid cell lines, thymocytes and activated T cells. In contrast, the cowpox virus protease inhibitor CrmA blocked Fas/ APO-1-transduced apoptosis, but did not affect cell death induced by γ-radiation or serum deprivation. Signalling through Fas/APO-1 did not down-regulate Bcl-2 or induce its antagonists Bax and Bcl-x(S). In Fas/ APO-1-deficient lpr mice, Bcl-2 transgenes markedly augmented..