Phosphorylation of Bcl-2 and mitochondrial changes are associated with apoptosis of lymphoblastoid cells induced by normal immunoglobulin G.

Abstract Normal human immunoglobulin G induces apoptosis in human lymphoblastoid cells which involves antibody-mediated Fas ligation and the activation of caspases. Here, we show that Bcl-2 is phosphorylated on serine upon treatment of CEM T cells with normal IgG and that the overexpression of Bcl-2 in stable transfectants of CEM T cells prevents IgG-induced cell death. Treatment of CEM cells with normal IgG also results in a reduction in mitochondrial transmembrane potential and in the release of cytochrome c (Cyt c ) into cytosol. The findings are concordant with earlier observations that apoptosis induced by IgG is associated with the activation of caspases. Our results demonstrate that Bcl-2 controls apoptosis induced by normal IgG and support a central role for Bcl-2 and mitochondria in antibody-mediated selection of lymphocyte repertoires.