Susceptibility of CBA/N Mice to Infection with Salmonella Typhimurium: Influence of the X-Linked Gene Controlling B Lymphocyte Function

Abstract

Abstract CBA/N mice have an X-linked immune defect that is associated with the absence of a subpopulation of mature or late developing B lymphocytes. The effect of this B cell defect on susceptibility of mice to Salmonella typhimurium was investigated. The 50% lethal dose (LD50) of S. typhimurium for CBA/N mice was 1000-fold less than for the immunologically normal, histocompatible CBA/CaHN strain. Genetic analysis revealed that the susceptibility of the CBA/N strain to S. typhimurium, like the immune defect, was X-linked since immune-defective F1 male mice derived from crosses between CBA/N and immunologically normal strains were susceptible to S. typhimurium (LD50 ≤ 20), whereas immunologically normal F1 males and females derived from these matings were resistant (LD50 ≥ 5 × 103). By contrast, both immune-defective and normal F1 mice were resistant to another facultative intracellular parasite, Listeria monocytogenes. Deaths among the immune-defective mice occurred primarily late in the course of infection (>10 days) whereas deaths of immunologically normal, S. typhimurium-susceptible strains (e.g., C57BL/6 and BALB/c) occurred early in the infectious process. To determine if the increased susceptibility of B cell-defective mice to S. typhimurium and the expression of the X-linked immune-deficiency gene (xid) were actually linked, F2 and backcross mice were phenotyped for the immune defect by measuring serum IgM levels and then challenged with the organism. Although no formal linkage was established, there was a close correlation between low serum IgM levels and susceptibility, since 93% of such mice succumbed to infection. These studies suggest that B cells play an important role in those events that govern the development of resistance to S. typhimurium late in the course of infection.