T cell autoimmunity in Ig transgenic mice

Autoantibodies directed at a diverse group of proteins of the U1/Sm ribonuc leoprotein (snRNP) are characteristic of systemic lupus erythematosus and a re found in the MRL murine model of this disease. This study examines the r ole of transgenic B lymphocytes in the regulation of autoreactive T cells t o the snRNP autoantigen, Transgenic mice were developed bearing an Ig heavy chain gene specific for the D protein component of murine snRNP, B lymphoc ytes in these mice are neither deleted nor anergic and are of an immature ( heat-stable Ag-high) phenotype, T lymphocytes from anti-snRNP transgenic mi ce were examined using a recombinant form of the D protein of the murine sn RNP complex, Our results revealed that transgenic anti-snRNP B cell APCs st imulated CD4 T cells from wild-type C57BL/6 and MRL lpr/lpr mice, while non specific APCs failed to stimulate CD4 T cells. This study demonstrates that autoreactive T cells are not deleted from wild-type mice, although their a ctivation is facilitated by autoantigen-specific APCs, The snRNP-reactive T cells in C57BL/6 transgenic mice are tolerized, in contrast to those T cel ls from MRL lpr/lpr transgenic mice. These studies implicate a role for aut oreactive B lymphocytes in the in vivo activation and/or diversification of autoreactive T cells.