Genetic control of the immune response to staphylococcal nuclease. VII. Role of non-H-2-linked genes in the control of the anti-nuclease antibody response

Abstract

Three weeks after immunization with staphylococcal nuclease in complete Freund''s adjuvant, strain A/J (H-2a) mice produced significantly higher titers of antibody than strain B10.A (H-2a) mice, whereas mice of strains A.BY (H-2b) and B10 (H-2b) produced barely detectable titers. With hyperimmunization, A/J and A.BY mice reached the same peak levels for antibody titers, both several-fold higher than those reached by B10.A and B10 mice. Analysis of the specificity of antibodies by assessment of binding to 2 fragments of nuclease showed similarities between strains of the same H-2 haplotype. Although H-2-linked genes determined initial responsiveness at 3 wk and the relative proportions of antibodies directed toward different antigenic determinants on the nuclease molecule, non-H-2-linked genes probably determined the overall magnitude of the hyperimmune response. Measurement of the affinity of the antibodies to the nuclease fragment (1-126) showed that strains B10 and B10.A produced antibodies with 7- to 10-fold higher affinity than comparable antibodies from strains A.BY and A/J. In a backcross of (B10.A .times. A/J) .times. B10.A, the level of antibody segregated independently of the Ig-1e CH [H chain constain region] allotype and the A/J anti-nuclease idiotypes. A gene(s) linked to neither H-2 nor H chain structural genes appears to control the aggregate response to antigenic determinants on the nuclease molecule independent of subspecificities of these antibodies or their idiotype.