Genetic Control of the Immune Response: the Effect of Non-H-2 Linked Genes on Antibody Production¹

In mice genetic control of the ability to form an immune response to the random terpolymer of glu⁶⁰, ala³⁰, tyr¹⁰ (GAT) is regulated by an Ir gene which maps between the K and Ss-Slp region of the H-2 complex. Several responder mouse strains were immunized with limiting doses of GAT. All responder strains produced GAT antibody after immunization with 1 µg, but not with 0.1 µg GAT. Although all responder strains responded to the same limiting doses of antigen, the serum concentrations of anti-GAT antibodies varied considerably among strains. Thus A, A.By and (B10 × A)F₁ mice demonstrated at least 10-fold higher GAT-binding capacities than B10 or B10.A mice. This dominant non-H-2 linked quantitative trait reflects differences in the concentration of specific antibody since anti-GAT antibodies from A and B10 mice were shown to have similar binding affinities, and inhibition studies with the copolymers GT and GA indicated that both the A and B10 antisera also had similar specificity. Measurements of antibody concentration have shown that sera from A strain mice contained 15-fold more specific antibody than sera from B10 animals. In addition, plaque assays demonstrated more antibody-forming cells in A strain animals.

Genetic analysis demonstrated that these strain differences were under multigenic control. One of the genetic components was shown to be linked closely with the heavy chain allotype loci.