Transgenic expression of Fas in T cells blocks lymphoproliferation but not autoimmune disease in MRL-lpr mice

Fas is a member of the TNF receptor family, Binding of Fas ligand to Fas induces apoptosis in Fas-bearing cells. Fas is expressed in various cells, including thymocytes, peripheral T cells, and activated B cells, The mouse lr mutation is a loss of function mutation of Fas, MRL-lpr/lpr mice develop lymphadenopathy and spIenomegaly, and produce multiple autoantibodies, which results in autoimmune disease. In this report, we describe the establishment of a line of Fas transgenic MRL-lpr mice in which mouse Fas cDNA was expressed using the T cell-specific murine lck promoter, The transgenic mice expressed functional Fas in thymocytes and peripheral T cells, but not in B cells, The transgenic mice did not accumulate abnormal T cells (Thy-1(+) B220(+)), but still accumulated B cells (Thy-1(-) B220(+)); they produced a large quantity of Igs (IgG1 and IgG2a), including anti-DNA Abs, and developed glomerulonephritis. These results suggest that autoreactice or activated B cells must be killed through Fas expressed in the B cells by the Fas ligand expressed in activated T cells.