X-Linked Genetic Control of Hapten-Polysaccharide-Mediated Specific Immune Unresponsiveness in CBA/N Mice

Abstract

CBA/N mice carry an X-linked recessive B cell defect which prevents them from making antibody responses to thymic independent antigens such as arsonate-, sulfonate-, or DNP-conjugated Ficolls. They do, however, make good plaque-forming cell (PFC) responses to the same haptens coupled to hemocyanin; thus, they do not selectively lack Ig receptors reactive with these haptens. When CBA/N mice are injected with DNP-Ficoll 1 or 2 hr before immunization with DNP-hemocyanin, their otherwise normal PFC response to this thymic dependent antigen is virtually abolished. As little as 10 ng of DNP-Ficoll can profoundly suppress the fourth day, direct PFC response to 50 µg of DNP-hemocyanin. Hence, the B cell defect that causes failure of CBA/N mice to respond to DNP-Ficoll is not associated with a failure to recognize this haptenated thymic independent antigen. The CBA/N susceptibility to haptenated Ficoll blockade is hapten specific. A similar type of hapten-specific blockade can be mediated by DNP-conjugated pneumococcal polysaccharide. This susceptibility to hapten-specific polysaccharide-mediated blockade occurs in the male but not the female hybrid offspring of defective CBA/N female mice. Hence, it is transmitted via the X chromosome and is recessive or has reduced penetrance in females. Our findings indicate that this X-linked vulnerability to hapten-specific, polysaccharide-mediated blockade probably represents a separate functional aspect of the basic X-linked recessive CBA/N defect which heretofore was recognized mainly as an inability to respond to most thymic independent antigens.