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The concentration of serum IgM molecules binding to IgG2a (rheumatoid factor [RF]) in solid phase assays is 10-100-fold higher in normal, unmanipulated C3H/HeJ (H-2k) than in C57BL/6 (H-2b) mice. Analysis of MHC-congenic mice with the prototype strains show that C3H SW (H-2b) are low, and B6.H-2k are high RF expressor strains, respectively. Furthermore, segregation of RF phenotypes in progenies from backcrosses to C3H/HeJ of (C3H/HeJ x C57BL/6)F1 hybrid mice shows MHC- and IgH-linked controls. RF phenotypes also segregate as if they are MHC linked in crosses between H-2-congenic strains (C3H/HeJ and C3H.SW). The study of intra-H-2 (k/b and k/s) recombinant mice suggested that RF phenotype control is linked to the I-E region. This was confirmed by the typing of C57BL/6 mice expressing a transgenic E alpha chain, and thus, I-E+, which, in contrast to nontransgenic littermates, are high expressors of RF.

I-E-linked control of spontaneous rheumatoid factor production in normal mice.