Polymorphism of age-related changes in the antibody response to the hapten phosphorylcholine

Aging is accompanied by changes in the immune system that occur at different levels and at different periods of time. We have studied age-related changes in isotype and idiotype of the antibody response to hapten phosphorylcholine (PC) in C57BL/6, and A mice and in the congenic MRL/Mp(-)+/+ and MRL/Mp-1pr/1pr strains. Three groups, representing young, middle and old age were immunized with PC-keyhole limpet hemocyanin. Total anti-PC antibody and the contribution of each isotype and of the T15 idiotype were assessed in the initial and late response. Some features of the antibody-response were similar in all the strains tested, e.g. the largest quantity of anti-PC antibody is formed in middle age and IgM is dominant in the initial response. However, remarkable differences occur in the isotype and idiotype predominance. Particularly, congenic MRL/Mp strains, prone to autoimmune disease, express the T15 idiotype only at low levels, even though IgM, which normally expresses this idiotype, is produced in large amounts. Furthermore, the late (memory) response of the MRL/Mp strains is dominated by IgG2b rather than IgG1, which is the predominant isotype in mice of long-lived strains. We conclude from these results that the number of T helper cells, involved in isotype regulation decreases with age and that there is a genetic variation, i.e., polymorphism in the ability to express T15-idiotype producing subtypes.