INTERVAL MAPPING OF QUANTITATIVE TRAIT LOCI CONTROLLING HUMORAL IMMUNITY TO EXOGENOUS ANTIGENS - EVIDENCE THAT NON-MHC IMMUNE-RESPONSE GENES MAY ALSO INFLUENCE SUSCEPTIBILITY TO AUTOIMMUNITY

IgG Ab titers elicited to bovine rhodopsin in CFA differ 8- to 10-fold between H2(c) identical inbred strains A.SW/snJ (high responder) and SJL/snJ (low responder), This variation in IgG Ab titer resulted from a dramatic difference in the rise in Ab titer occurring during the mat uration of the T-dependent humoral immune response. To determine the p ositions of non-MHC genes controlling this quantitative variation in T -dependent humoral immune responsiveness, 206 reciprocal (A.SW/snJ x S JL/snJ)F-2 female progeny were immunized and assayed for anti-rhodopsi n responsiveness. The genomes of these progeny were screened with 115 polymorphic simple sequence repeat markers covering >90% of the mouse genome, Interval mapping analysis localized the positions of these non -MHC immune response genes to genomic intervals on chromosomes 1, 5, a nd 13, Interestingly, these three intervals coincide exactly with thre e intervals recently shown to contain genes contributing to susceptibi lity to systemic lupus erythematosus and/or the production of autoimmu ne anti-dsDNA Abs, These results suggest that some genes affecting lev els of humoral immune responsiveness to exogenous Ag may also play a r ole in genetic susceptibility to humoral autoimmune diseases, Analyses of the modes of inheritance demonstrated that high responder alleles were inherited from both parental genomes, indicative of epistatic int eractions among genes influencing humoral immune responsiveness.