Rheumatoid factors in 129XB recombinant inbred strains. Igh-1-linked control of allotypic and isotypic specificities.
To examine the role of autologous IgG in the induction of murine rheumatoid factors (RF) we have analyzed the allotypic specificity of anti-IgG2a RF in recombinant inbred strains derived from 129/Sv (Igh-1a) and C57BL/6 (Igh-1b) mice. In five of six Igh-1a strains, anti-IgG2a RF reacted with IgG2aa but failed to react with IgG2ab. In contrast, isotype-specific RF, which reacted equally well with a and b allotypes of IgG2a, represented the major RF species in one Igh-1a and all five Igh-1b strains tested. An additional form of RF specific for IgG2ab and not reactive with IgG2aa was detected in one Igh-1b strain. RF specific for a give allotype was thus only found in the presence of that allotype, which strongly suggests the involvement of autologous IgG in the induction of mouse RF synthesis. The specificity of RF was apparently further controlled by genes linked to but different from the Igh-C locus, as indicated by the absence of IgG2aa-specific RF in one of the 6 Igh-1a strains tested. Because this strain, 129XBG, has been shown to express idiotypic markers characteristic of Igh-1b mice, it is likely that the genes, which in the presence of a given allotype induce the production of isotype rather than allotype-specific RF, are identical to those that control the expression of idiotypes. Evidence was also obtained to indicate that Igh-1-linked genes influence the isotypic specificity and the isotype of RF itself: IgA anti-IgG2a predominated in Igh-1a strains and IgM anti-IgG1 in Igh-1b strains. Interestingly enough, total IgA and IgG2a levels also were higher in Igh-1a than in Igh-1b strains.
D000818:Animals; D000918:Antibody Specificity; D005260:Female; D008040:Genetic Linkage; D007070:Immunoglobulin A / Q000032:analysis; D007126:Immunoglobulin Allotypes / Q000235:genetics*; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000502:physiology; D007075:Immunoglobulin M / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011995:Recombination, Genetic; D012217:Rheumatoid Factor / Q000032:analysis / Q000096:biosynthesis*
D007070:Immunoglobulin A; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D012217:Rheumatoid Factor