Typhoid fever and nontyphoidal bacteremia caused by Salmonella remain critical human health problems. B cells are required for protective immunity to Salmonella, but the mechanism of protection remains unclear. In this study, we immunized wild-type, B cell-deficient, Ab-deficient, and class-switched Ab-deficient mice with attenuated Salmonella and examined protection against secondary infection. As expected, wild-type mice were protected and B cell-deficient mice succumbed to secondary infection. Interestingly, mice with B cells but lacking secreted Ab or class-switched Ab had little deficiency in resistance to Salmonella infection. The susceptibility of B cell-deficient mice correlated with marked reductions in CD4 T cell IFN-γ production after secondary infection. Taken together, these data suggest that the primary role of B cells in acquired immunity to Salmonella is via the development of protective T cell immunity.
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