Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti-DNA autoantibodies

Osteopontin (OPN) is an Arg-Gly-Asp-containing phosphoprotein that is secre ted by activated T cells. The concentration of serum OPN protein is elevate d in autoimmune-prone MRL-lpr mice as well as in patients with systemic lup us erythematosus. Previously, it was shown that OPN induces the polyclonal activation of B cells, resulting in the augmented production of immunoglobu lin, indicating that OPN plays some role in the development of autoimmune d isease. However, the link between OPN and development of autoimmune disease remains unclear. To analyze the role of OPN in immune system and autoimmun e diseases, we have generated two kinds of transgenic mice: one carries the immunoglobulin (Ig) enhancer/SV40 promoter and the other carries the cytom egalovirus enhancer/chicken beta-actin (CAG) promoter. In both groups of tr ansgenic mice, the B1 cell population in peritoneal cavity was markedly inc reased and titer of IgM and IgG(3) antibodies in the serum was considerably higher than that in wild-type mice. Most important, the titer of the IgM c lass of anti-double-stranded DNA antibody was significantly elevated in tra nsgenic mice. These results strongly suggest that OPN may have an important role in the propagation and differentiation of B1 cells and production of autoantibodies.