Genetic control of resistance to mercury-induced immune/autoimmune activation

Previous studies have shown that genetic factors control the susceptibility to mercury-induced immunoglobulin (Ig)Gl antibody formation, IgE synthesis , renal IgG deposits and antinucleolar autoantibodies (ANolA) production in the susceptible mice. In this study, we examined the genetic control of re sistance to these characteristics after HgCl2 injection in Fl hybrid crosse s between the highly mercury resistant DBA/2 and mercury susceptible NZB (H -2(d)), SJL (H-2(s)), A.CA (H-2(f)) and DBA/I (H-2(q)) mice and also in bac kcross hybrids between (DBA/2 x SJL)Fl and SJL mice. We observed that mercu ry-induced immune/autoimmune manifestations were profoundly downregulated i n most (if not all) of the Fl hybrids, indicating that the resistance to me rcury was a dominant trait. Analysis of mercury-induced immune/autoimmune r esponses in the (DBA/2 x SJL) x SJL backcross hybrids suggested that only o ne gene or a cluster of genes determined the resistance to the ANolA produc tion, whereas the resistance to ether characteristics was controlled by two and/or three gene loci. By H-2 genotyping the backcross mice, it was found that H-2d haplotype per se could confer resistance to ANolA production. Ho wever, we did not find any significant association between the H-2d haploty pe and the resistance to increase of IgGl and IgE synthesis and the develop ment of renal IgGl deposits. Thus, while in DBA/2 mice, gene(s) in the H-2 loci strictly contribute to the inheritance of resistance to ANolA producti on; non-H-2 genes mainly govern the inheritance of unresponsiveness regardi ng other characteristics.