Characterization of Murine Brain-Reactive Monoclonal IgG Autoantibodies

Abstract

A diversity of brain-reactive autoantibodies (BRAA) is found in the sera and cerebrospinal fluid in elevated amounts in systemic lupus erythematosus (SLE) and correlates with some CNS manifestations of both human and murine SLE. In order to test the hypothesis that BRAA mediate the CNA manifestations, we are developing a library of brain-reactive monoclonal autoantibodies (BRMA) from autoimmune mice for characterization. We have recently reported on the production of BRMA of the IgM class from unimmunized autoimmune mice. In the current study we extend our investigations and report on the production and characterization of two BRMA of the IgG class. These antibodies react against integral brain membrane antigens of approximately 58, 32, and 30 kDa by immunoblot. Reactivity to such antigens is also found in a majority of the autoimmune murine serum samples tested, but not in nonautoimmune mice. These IgG BRMA show reactivity to cell bodies of the cerebral cortex, hippocampus, and hypothalamus of murine brain but not to fiber tracts. They also react with an integral thymus membrane antigen, but not to antigens of other tissues tested. Because of their properties, BRMA such as those characterized here are likely to be of pathogenic significance in CNS involvement in SLE.