Polygenic control of antibody production and correlation with vaccine induced resistance to rabies virus in high and low antibody responder mice

Abstract

The amplification of 'high' (H) and 'low' (L) multispecific antibody responses achieved respectively by H and L lines of selection GP represents a valuable tool in the genetic study of host-infection interactions. These lines were obtained by bidirectional selective breeding for high (H(GP)) or low (L(GP)) antibody production to natural complex antigens. H(GP) and L(GP) parental lines and reciprocal F1 hybrids, as well as their F2 segregants and backcrosses were submitted to immunization and challenge with rabies virus CVS strain. Acquired resistance was 1000-fold higher in H(GP) than L(GP) mice, with a dominance effect to low antibody production observed in F1 hybrids. An association between high antibody response and acquired resistance (P < 0.001) in F2 segregant mice was noticed. The genetic study was performed in these several populations, with a single dose of 104.5- fold LD50 CVS. We could demonstrate 3 independent loci regulating the anti- rabies antibody production, that are distinct, at least in part, from the 10 genes controlling the antigen selection response (sheep erythrocytes) of selection GP.