Background: The eradication of facultative intracellular bacterial pathogens, like Salmonella typhi, requires the concerted action of both the humoral immune response and the cytotoxic CD8 + T cell response. Dendritic cells (DCs) are considered to orchestrate the cytotoxic CD8 + T cell response via cross-presentation of bacterial antigens onto MHC class I molecules. Cross-presentation of Salmonella by DCs however, is accompanied by the induction of apoptosis in the DCs. Besides antibody production, B cells are required to clear Salmonella infection for other unknown reasons. Methodology/Principal Findings: Here we show that Salmonella-specific B cells that phagocytose Salmonella upon BCRligation reactivate human memory CD8 + T cells via cross-presentation yielding a Salmonella-specific cytotoxic T cell response. The reactivation of CD8 + T cells is dependent on CD4 + T cell help. Unlike the DCs, B cell-mediated crosspresentation of Salmonella does not coincide with apoptosis. Conclusions/Significance: B cells form a new player in the activation of the cytotoxic effector arm of the immune respons
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