Studies of congenic MRL-Ipr/Ipr.xid mice.
Highly inbred MRL-Ipr/Ipr.xid congenic mice were bred and compared with their + littermates. The xid-bearing congenics developed lymphadenopathy consisting of dull Ly-1+ T cells and impairment of cellular proliferation and IL 2 production in response to the T cell mitogen Con A. Thus, the lpr gene was fully expressed. The xid gene, however, was also expressed as indicated by the failure to respond to immunization with TNP-Ficoll and flow cytometric analysis of splenic B cells. The xid gene was associated with a marked reduction in IgM anti-ssDNA and anti-nDNA of both classes, and serum Ig-bound gp 70. Kidney disease was markedly retarded as was death from the autoimmune process. These studies suggest that the T cell lymphoproliferation and dysfunction characteristic of MRL-Ipr/Ipr mice is not sufficient to induce accelerated autoimmunity; xid is able to markedly slow the process. The xid gene interferes with the development of a B cell subset necessary for maximum autoantibody production, anti-gp 70 production, and the resultant immune complex renal and cardiac disease. The present finding of protection against accelerated autoimmunity in MRL-Ipr/Ipr mice by xid, coupled with previous demonstrations of protection against autoimmunity in other autoimmune mouse strains, suggests that a common approach to the therapy of systemic lupus may be possible.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000235:genetics; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000235:genetics; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics* / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D005808:Genes, Recessive; D005921:Glomerulonephritis / Q000209:etiology / Q000473:pathology; D006023:Glycoproteins / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000276:immunology; D008206:Lymphatic Diseases / Q000235:genetics / Q000503:physiopathology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D011507:Proteinuria / Q000209:etiology / Q000235:genetics
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C033589:glycoprotein gp70, murine serum