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H-2-linked control of the Yaa gene-induced acceleration of lupus-like autoimmune disease in BXSB mice

Merino, Ramon
Fossati-Jimack, Liliane
Lacour, M.
Higaki, M.
Published in European Journal of Immunology. 1992, vol. 22, no. 2, p. 295-299
Abstract The accelerated development of lupus-like autoimmune disease in male BXSB mice (H-2b, I-E-) is associated to the presence of a mutant gene, designated Yaa, located on their Y chromosome. To investigate whether the H-2b haplotype and/or the lack of expression of I-E molecules play any role in the Yaa-linked acceleration of autoimmune disease, an I-E+ BXSB.H-2d congenic strain was created by backcross procedures. We compared the development of autoimmune disease in the novel BXSB.H-2d (I-E+) strain to that of BXSB.H-2b (I-E-) and BXSB.H-2b/d (I-E+) heterozygous mice. Male BXSB.H-2d (I-E+) mice exhibited only a limited production of autoantibodies and a lower incidence of glomerulonephritis with a markedly prolonged survival rate, which were essentially identical to those of female BXSB mice of both-H-2b and H-2d haplotypes. However, BXSB.H-2b/d (I-E+) heterozygous males developed an accelerated disease comparable to that of conventional BXSB.H-2b (I-E-) male mice. These results indicate that the expression of I-E molecules and consequent clonal deletion or anergy of I-E reactive T cells does not appear to be responsible for the prevention of accelerated autoimmune disease in BXSB.H-2d (I-E+) male mice. The finding that the Yaa gene-induced acceleration of lupus-like autoimmune disease is modulated by gene(s) within or closely linked to the H-2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.
Keywords AnimalsAntigens, Surface/analysisAutoimmune Diseases/ geneticsFemaleGenesGenes, MHC Class IIH-2 Antigens/ geneticsHistocompatibility Antigens Class II/ geneticsLeukocytes, Mononuclear/immunologyLupus Erythematosus, Systemic/ geneticsMajor Histocompatibility ComplexMaleMiceMice, Inbred StrainsY Chromosome
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PMID: 1537372
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