Genetically conferred defect in anti-Salmonella antibody formation renders CBA/N mice innately susceptible to Salmonella typhimurium infection.

Abstract

The differential sensitivity of inbred mice to Salmonella typhimurium, the agent of murine typhoid, is controlled by at least 3 distinct genetic loci: Ity(s), and xid. The X-linked gene, xid, renders CBA/N mice and F 1 male mice derived from CBA/N females salmonella susceptible and B cell defective. The mechanism of xid-conferred susceptibility to salmonellosis was investigated. A comparison of the early net growth of S. typhimurium in the spleens of Ity(s) and xid mice indicated that, unlike the salmonella sensitivity of Ity(s) mice, the susceptibility of immune defective (CBA/N x DBA/2N)F 1 male mice (F 1 male mice) could not be attributed solely to the failure of reticuloendothelial cell organs to contain multiplication of the bacterium. Moreover, the t cell-dependent delayed hypersensitivity responses of F 1 male mice and immunologically normal F 1 littermates to S. typhimurium were similar. Therefore, the humoral response of F 1 male mice to salmonellae was examined. IgM anti-S typhimurium antibodies were produced by F 1 male mice and immunologically normal F 1 female littermates after immunization with a killed preparation of the bacterium. In contrast, although high titers of IgG anti-salmonella antibodies were demonstrable in the sera of F 1 female mice by 3 wk post-vaccination, only low titers of IgG antibodies were observed in F 1 male sera at that time. Moreover, the resistance of F 1 male mice to S. typhimurium was markedly increased by passive transfer of immune F 1 female serum. The protective substance in F 1 female serum appeared to be anti-salmonella antibody, since it was present in the gamma-globulin fraction of the serum and could be removed by adsorption with the bacterium. The resistance of F 1 male mice to S. typhimurium was also enhanced by reconstitution with immunologically normal F 1 bone marrow cells. Taken together, these findings suggest that the innate S. typhimurium susceptibility of CBA/N mice is primarily a consequence of their delayed and diminished antibody response to the organism.