Genetic and Cellular Factors in the Immune Response

Abstract

Abstract The antibody response to poly Glu52Lys32Tyr15 was studied in two inbred strains of rats, the highly responding ACI strain and the poorly responding F344 strain. The amounts of antibody formed by the parental strains, the F1 and F2 generations and the backcrosses into the parental strains were assayed by a quantitative immunoadsorbent micro-method. Radio-immunoelectrophoretic studies showed that the antibody response was distributed among the IgM, γ1 and IgG immunoglobulin classes in both males and females. There was no correlation between the quantity of antibody made and the immunoglobulin class. The results of the experiments are consistent with a model in which the genetic control of the antibody response is exercised by at least two independently segregating genes—one for recognition of antigen (R-gene) and one for quantitative control of the amount of antibody formed (Q-gene). In addition, there is a sex influence, which is most clearly seen in the highly responding ACI parental strain and in backcrosses to that strain; it is progressively diminished by increased cross-breeding. The functioning of the sex factor is associated with a higher and more heterogeneous antibody response in females. The effect of antigen dose was studied systematically over a range of 104. The ACI strain made more antibody as the dose of antigen was increased, and the response reached a plateau following immunization with 1.5 mg of antigen. On the other hand, the response in the F344 strain was low and erratic up to a dose of 1.5 mg of antigen; thereafter, the antibody response slowly increased, and all animals made antibody. At very low doses of antigen, the ACI strain made predominantly IgM antibody, and, as the antigen dose increased, all classes of immunoglobulin contained antibody. In contrast, the F344 strain always formed predominantly IgG antibody and very little, if any, IgM antibody. Aggregation of the antigen with methylated bovine serum albumin had different effects on the antibody response in the two strains of rats. The amount of antibody formed by the highly responding ACI strain was decreased or unchanged. The amount of antibody formed by the poorly responding F344 strain was either increased or unaltered. The antibody formed by the F344 strain was almost exclusively in the IgG class, whereas the ACI strain formed antibody in all immunoglobulin classes. The various hybrids of the ACI and F344 strains responded predominantly in the IgG class, in contrast to the findings following immunization with the unaggregated antigen, in which case the antibody response was distributed among all of the immunoglobulin classes. These findings suggest that an inability to make IgM antibody to poly Glu52Lys33Tyr15 may be a factor in the poor response of the F344 strain to immunization with that antigen. The heterogeneity in the magnitude of the antibody response in the ACI strain was greatly restricted, and all animals in the F344 strain responded. Finally, the sex difference in the antibody response was unaltered or enhanced.