Contribution of H-2 and non-H-2 genes in the control of mercury-induced autoimmunity.
Mercury-induced autoimmunity is characterized by a T cell-dependent B cell activation (mainly of IgG1 and IgE isotypes), production of anti-nucleolar autoantibodies (ANolA) and the formation of renal IgG deposits. The autoimmunity is to a large extent controlled by genetic factors. We studied 15 different inbred mouse strains of seven H-2 (mouse MHC) genotypes to determine the importance of H-2 and non-H-2 background genes in mercury-induced autoimmunity. The tested strains exhibited a diverse autoimmune response to mercury. In each H-2 genotype, there was at least one strain which responded to mercury by the production of high levels of IgG1 and IgE Ig as well as by the development of high titers of renal IgG1 deposits. Only mouse strains with H-2(s) and H-2(q) genotypes, irrespective of their background genes, produced ANolA after mercury treatment. Only SJL (H-2(s)) and A.SW (H-2(s)) mice were highly susceptible to all characteristics of mercury-induced autoimmunity. NZB (H-2(d)) mice were also highly susceptible, but they did not develop ANolA. Only the DBA/2 (H-2(d)) strain was found to be resistant to all tested mercury-induced autoimmune manifestations, suggesting that non-responsiveness to mercury in DBA/2 mice was largely influenced by non H-2 genes. These findings imply that H-2 genes mainly determine the susceptibility to mercury-induced ANolA production, whereas non-H-2 genes control the susceptibility to and the severity of the B cell activation and renal IgG deposition.
Abedi-Valugerdi
M
M
Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, 10691 Stockholm, Sweden.
Möller
G
G
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D015551:Autoimmunity / Q000187:drug effects*; D002466:Cell Nucleolus / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006183:H-2 Antigens / Q000235:genetics*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008297:Male; D008628:Mercury / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity
D000974:Antibodies, Antinuclear; D006183:H-2 Antigens; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D008628:Mercury