Interstrain variations in nephritogenicity of heterologous protein in mice.

Swiss albino, BALB/c, and eight substrains of C3H mice were given daily intraperitoneal injections of horse apoferritin (HAF) for up to 56 days. At varying intervals, renal tissue was examined by light, immunofluorescence, and electron microscopy. Swiss mice developed proliferative glomerulonephritis after 7 to 14 days of HAF, and 45 per cent progressed to severe crescentic glomerulonephritis after from 21 to 56 days of HAF. In Swiss mice, glomerular immune deposits evolved from predominantly IgM mesangial deposits at 7 days to mesangial IgG at 14 days to capillary wall IgG after 21 or more days of HAF injections. BALB/c mice given identical HAF doses never developed severe crescentic glomerulonephritis but rather an extensive global necrotizing glomerulonephritis most prevalent after from 9 to 18 days of HAF. The distinct evolution of glomerular immune deposits observed in Swiss mice was less clear-cut in BALB/c mice, with greater persistence of mesangial deposits and IgM over time. Only 11 per cent of C3H mice (confined to two substrains) developed glomerular lesions by light microscopy after 2 to 3 weeks of HAF administration. No C3H/HeN mice developed glomerulonephritis even after up to 47 days of HAF injection. From 7 days on, 45 per cent of HAF-injected C3H mice had low level IgM mesangial immune deposits but did not manifest the evolution from mesangial to capillary deposition observed in BALB/c and Swiss albino mice. F1 hybrid and congenic mice carrying BALB/c H-2 genetic information developed glomerular lesions similar to those produced in BALB/c mice. These data (1) indicate an interrelated morphologic and immunohistologic evolution of heterologous protein induced glomerular lesions in mice, (2) demonstrate morphologic and immunohistologic differences in glomerular lesions development between genetically disparate mouse strains given identical antigen exposures, and (3) support the genetic control of heterologous protein-induced glomerulonephritis and suggest a role for the major histocompatibility region in this genetic regulation.