Localization of covalent immune complexes on the epithelial side of the glomerular basement membrane in mice.

The site of immune complex localization in human glomerulonephritis is important in determining the kind of disease that may develop. Immune complex deposits found on the subepithelial side of the glomerular basement membrane are characteristic of membranous nephropathy, a common and often severe form of human renal disease. The pathogenesis of this disease remains controversial and arguments have recently been put forward that the subepithelial deposits arise from an in situ mechanism. This mechanism involves the initial localization of antigen allowing the antibody to subsequently combine, i.e. the immune complex is formed locally. This mechanism is thus in contrast to that in which immune complexes formed in the circulation are localized in the glomeruli. Covalent immune complexes do not dissociate and hence are ideal tools for studies to investigate whether complexes are able to cross the glomerular basement membrane. Covalent immune complexes of defined size and antigen-antibody ratio were prepared with a monoclonal antibody and photoaffinity labelling antigen, 4-azido-2-nitro-phenylated bovine serum albumin. When these complexes were injected into mice, complexes of 550,000 MW molecular weight (but not those of 800,000 MW) were shown by electron microscopic autoradiography to localize on the subepithelial side of the glomerular basement membrane. It is thus proposed that small circulating immune complexes may be important in the pathogenesis of subepithelial deposits and there is a need for devising reliable tests for measuring small immune complexes.