Non-H-2 genes alter the H-2 determined susceptibilities in immune complex nephritis.
These experiments examined the effects of genes outside of the H-2 region on disease susceptibility and pathogenesis. Four strains of mice with the susceptible H-2 type, H-2d, but different non-H-2 genes were studied. B10, D2, Balb/c, NZB, and DBA/2J mice were injected with 4 mg of apoferritin i.p. q.d. for 28 days. B10, D2 and Balb/c mice developed proliferative and crescentic glomerulonephritis. NZB mice developed proliferative and crescentic glomerulonephritis with wire loop lesions suggestive of lupus. DBA/2J mice developed only minimal mesangial proliferation without crescents or necrosis. Electron microscopy showed subepithelial and mesangial deposits in B10, D2, moderate subepithelial and mesangial deposits in Balb/c, and marked mesangial, subendothelial and subepithelial deposits in NZB. Immunofluorescence demonstrated the presence of IgG, IgM, C3 and apoferritin in these deposits. The DBA/2J mice had only minimal mesangial deposits by immunofluorescence and electron microscopy. These experiments demonstrate that non-H-2 genes alter the H-2d determined disease susceptibility seen in H-2 congenic mice. NZB genes can alter the disease so that lupus-like lesions develop and DBA/2J genes can substantially ameliorate the disease.
Frymoyer
P A
PA
Department of Medicine, SUNY Health Sciences Center, New York.
Connor
B J
BJ
Tatum
A H
AH
Gavalchin
J
J
D000818:Animals; D001052:Apoferritins / Q000276:immunology; D005455:Fluorescent Antibody Technique; D005796:Genes / Q000276:immunology*; D005805:Genes, MHC Class I / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000235:genetics* / Q000276:immunology; D007105:Immune Complex Diseases / Q000235:genetics* / Q000276:immunology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron
D001052:Apoferritins