Genetic control of B cell function. III. IgVH-controlled polymorphism in the frequencies of B cells that recognize xenogeneic red blood cells.
Previous work has shown that the primary IgM plaque-forming cell response of inbred mice to xenogeneic red blood cells (RBC) including sheep, horse and chicken RBC is under the control of two polymorphic genes or sets of genes, one linked to the Igh linkage group and the other of unknown linkage but unlinked to H-2 and a variety of other known genetic markers. Both genes together control B cell function but do not influence the function of T cells and macrophages. Thus, this system permits the study of two polymorphic loci that control B cell responsiveness. In this study we analyze the role of the Igh region in further detail. In bulk cultures and limiting dilution experiments, we confirm its exclusive influence on B cells also when analyzed separately from the background gene, i.e. in Igh-congenic strains. Moreover, we find in the majority of experiments 4-5-fold differences in sheep RBC-specific B cell precursor frequencies among lipopolysaccharide-reactive cells from 3 pairs of Igh-congenic high and low-responder strains. Similar frequency differences exist for horse RBC and chicken RBC-specific B cells but not for B cells with specificity for (4-hydroxy-5-iodo-3-nitrophenyl)acetyl (NIP)-gelatine. These differences are independent of the frequencies of B cells responding to lipopolysaccharide which are shown to be equal between Igh-congenic pairs of strains. Since the differences in RBC-specific B cell frequencies closely resemble the differences in bulk culture responses to the corresponding RBC, we conclude that the role of the Igh linkage group in controlling responsiveness to RBC lies in a selective influence on the B cell repertoire concerning precursor cells for RBC specificity. In addition, we find that the VH part of Igh is responsible for the observed frequency differences, suggesting that VH germ-line genes directly influence the composition of the mature B cell repertoire.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002645:Chickens / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011110:Polymorphism, Genetic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell