Genetic regulation of hypergammaglobulinaemia and the correlation to autoimmune traits in (NZB X NZW) F1 hybrid.

To determine the inheritance patterns of both IgM class and IgG class hypergammaglobulinaemias, the locations of genes and the relations of these genes to other autoimmune traits in NZB X NZW (B/W) F1 hybrid, we measured serum levels of both IgM and IgG in NZB, NZW, B/W F1 hybrid, B/W F1 X NZW back-cross and B/W F1 X NZB back-cross mice. The highest serum IgM levels were observed in NZB mice, however the serum IgG levels were normal. In contrast, a large amount of IgG was produced in B/W F1 hybrids, in which the serum IgM levels were lower than those observed in NZB mice. The NZW mice had fairly normal values for both measures. Progeny studies suggested that a single dominant locus (Imh-1) of NZB strain, which is loosely linked to brown-black coat colour locus b and Mup-1 locus on chromosome 4, determines the IgM class hypergammaglobulinaemia. The estimated gene order was Mup-1:b:Imh-1. This IgM class hypergammaglobulinaemia in NZB mice was suppressed to a considerable extent in B/W F1 hybrid mice by either a gene dosage effect or more likely, a regulatory gene locus of NZW strain, being also loosely linked to Mup-1 locus on chromosome 4. As for the IgG class hypergammaglobulinaemia, a complementary effect of two or three genes, either one or two dominant genes derived from NZB and a single dominant gene from NZW strains, determines this trait in B/W F1 hybrid mice. There appeared to be no relationships between the genes responsible for the IgM class and IgG class hypergammaglobulinaemias. When looking at the correlations between the hypergammaglobulinaemias and the traits, anti-double stranded DNA (dsDNA) antibodies and renal disease in both back-cross mice, we found a significant quantitative correlation only between the IgG class hypergammaglobulinaemia and the IgG class anti-dsDNA antibodies in B/W F1 X NZB back-cross mice.