Polyvalent antigen-antibody interactions are required for the formation of electron-dense immune deposits in passive Heymann's nephritis

Abstract

In order to analyze the initial steps involved in the formation of subepithelial electron-dense immune deposits, the authors induced passive Heymann's nephritis in rats by intravenous injection of monoclonal or polyclonal antibodies to the relevant antigen, a 330,000-dalton brush border protein also expressed within coated pits of glomerular epithelial cells. Whereas both mono- and polyclonal antibodies induced deposits detectable by indirect immunofluorescence, electron-dense deposits were only found in glomerular capillary walls of rats injected with polyclonal antibodies. Immunoultrastructural analysis confirmed the subepithelial location of heterologous IgG: monoclonal antibodies were essentially confined to the coated pits of glomerular epithelial cells, whereas polyclonal antibodies were detected in coated pits and in the subepithelial electron-dense deposits. In the face of an excess of circulating antibody, gp 330 was not detectable in the deposits, but a striking increase in the number of endoplasmic reticula positive for gp 330 was found. The results indicate that highly cross-linked immune complexes formed by polyvalent antibodies on the epithelial cell surface are necessary for the induction of subepithelial electron-dense deposits.