Immune complex disease. VI. Some determinants of the varieties of glomerular lesions in the chronic bovine serum albumin-rabbit system.

Glomerular lesions were evaluated by light, electron, and immunofluorescence microscopy in rabbits given daily injections, for prolonged periods of time, of either 12.5 mg. of bovine serum albumin (BSA) (group I) or increasing doses of BSA, paralleling the immune response (group II). In animals clearing 12.5 mg. or more of BSA per day (excluding those dying of anaphylaxis or unknown causes), marked differences were noted in the incidence of membranous glomerulonephritis (GLN) (50 per cent in group I versus 15.4 per cent in group II), of crescentic GLN (none in group I versus 26.9 per cent in group II), and of mesangiopathic GLN (11.1 per cent in group I versus 30.8 per cent in group II). On the basis of these variations and immunofluorescence microscopy findinds, it is concluded that the occurrence of membranous GLN is favored by the presence in the circulation of small concentrations of soluble immune complexes, whereas crescentic GLN results from the presence of high concentrations of such complexes. When BSA injections were discontinued in group I animals having membranous GLN, the immune deposits were sequestered by membranous transformation so that they were not readily solubilized by injections of large amounts of BSA; one such animal developed crescentic GLN. The observation that BSA was difficult to detect in the lesions of mesangiopathic GLN suggests that this lesion results from the deposition of complexes formed at equivalence or in antibody excess.