Most forms of glomerulonephritis are initiated by immune complex-mediated injury. Immune complex deposition in the glomerulus has been shown to result from both in situ formation and trapping of circulating immune complexes. It is the purpose of this proposal to investigate the role of an additional mechanism of glomerular immune complex formation. It is suggested that in the Heymann rat model of membranous nephropathy, a circulating antigen binds to a glomerular antigen via internal images. Immunization with the circulating antigen results in production of primary antibody and anti-idiotypic antibody. A subset of the anti-idiotypic antibodies will bear the appropriate internal image, will mimic the immunizing antigen, and thus will bind to the glomerular antigen. To investigate this hypothesis, the 2 antigens and primary and anti-idiotypic antibodies will be isolated and their binding via internal images will be determined. Demonstration that a circulating antigen binds to a glomerular antigen with subsequent antibody deposition would explain the subepithelial localization of immune deposits in membranous nephropathy. In addition, the production of anti-idiotypic antibodies that mimic antigen has been postulated to contribute to the development of autoimmunity. Confirmation of the internal image relationships in the putative antigens of Heymann nephritis offers the opportunity to evaluate this postulate.
