Genetic control of the humoral immune response to rabbit erythrocyte isoantigens

Blood group Hg^A negative rabbits were injected with 2 × 10⁹ Hg^A positive erythrocytes from a donor rabbit. Assortative matings were set up between those rabbits which produced detectable anti-Hg^A (responders) and those which did not (non-responders). The progeny were injected with 2 × 10⁹ Hg^A positive erythrocytes 3 months after birth and their anti-Hg^A response measured. It was found that 20/24 (83 per cent) of the offspring of responder parents, but only 4/26 (15 per cent) of the offspring of non-responder parents, produced detectable anti-Hg^A. No difference was found between the ability of responders and non-responders to produce haemagglutinins to various doses of sheep erythrocytes. In contrast, non-responder rabbits rarely responded to non-Hg^A blood group isoantigens on the donor erythrocytes whereas rabbits which responded to Hg^A after injection of the donor erythrocytes often responded to non-Hg^A isoantigens. Typing the cells of non-responder rabbits with the sera from responder rabbits containing non-Hg^A antibodies showed that the non-responder cells were antigenically more like the donor cells than were the cells from responder rabbits. The ability to respond to Hg^A was not associated with any particular heavy or light chain immunoglobulin allotype specificities. It is considered that Hg^A has an important helper function in regard to the antibody response to non-Hg^A antigens but the latter probably also have a similar but less marked effect in relation to the Hg^A antibody response. The genetic control observed is thought to operate through T cell recognition and reaction with Hg^A and other blood group determinants.