Allogeneic MHC antigen requirements for lupus-like autoantibody production and nephritis in murine graft-vs-host disease.
A graft-vs-host (GVH) reaction of parental T cells in allogeneic F1 mice can lead to an autoimmune disease resembling human SLE. We analyzed the contribution of MHC genes to the development of IgG antinuclear antibody production and immune complex glomerulonephritis in MHC-congenic F1 recipients. DBA/2 T cells elicited IgG antibodies to histone, ssDNA, and dsDNA in all histoincompatible F1 recipients that were studied. The anti-DNA antibody responses were quantitatively similar among the F1 combinations and displayed comparable IgG2a subclass and cationic charge characteristics. In contrast, severe renal disease was manifested only in F1 mice that expressed H-2b encoded class II gene products. Disease susceptibility was associated with a decrease in circulating anti-DNA antibodies and a characteristic localization of immune complexes in the glomeruli. The data suggest that the production of potentially pathogenic IgG anti-nuclear antibodies is not sufficient for the development of renal disease in GVH-induced lupus. Thus, another event separate from autoantibody production is MHC dependent and appears to be critical for the formation and/or deposition of pathologic immune complexes.
Portanova
J P
JP
Department of Medicine, VA Medical Center, Denver, CO.
Ebling
F M
FM
Hammond
W S
WS
Hahn
B H
BH
Kotzin
B L
BL
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis*; D003165:Complement System Proteins / Q000378:metabolism; D003433:Crosses, Genetic; D004247:DNA / Q000276:immunology; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000150:complications / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D006657:Histones / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D008181:Lupus Nephritis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D006183:H-2 Antigens; D006657:Histones; D007074:Immunoglobulin G; D003165:Complement System Proteins; D004247:DNA