A potential role for microbial superantigens in the pathogenesis of systemic autoimmune disease

Abstract

We have attempted herein to demonstrate how microbial superantigens could promote an abnormal form of "cognate" T helper-B cell interaction, analogous to that which may occur during GVH disease, leading to B cell activation and systemic autoimmunity. In vitro studies performed at our laboratory and others have demonstrated that resting human B cells bind microbial superantigens and present them to superantigen-reactive autologous T helper cells, resulting in T cell activation and polyclonal IgM and IgG production by the superantigen-bearing B cells. In vitro studies of microbial superantigen-mediated murine T helper-B cell interactions demonstrate preferential help for B cells that have encountered specific antigen. Both in humans and in mice, the cellular interactions involved and the B cell responses induced are highly analogous to those mediated by allospecific T helper-B cell interaction. Finally, the results of studies carried out on T cell-deficient (nude) mice suggest that microbial superantigens may trigger similar T helper cell-dependent polyclonal IgM and IgG responses in vivo. These mice will be studied over time and tested for the development of autoantibodies characteristic of SLE and of autoimmune organ system damage, the occurrence of which are predicted by our model.