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Antigen-Specific B Cells Reactivate an Effective Cytotoxic T Cell Response against Phagocytosed Salmonella through Cross-Presentation 1 1 1 1 1 2 Jelle de Wit , Yuri Souwer , Tineke Jorritsma , Hanny Klaasse Bos , Anja ten Brinke , Jacques Neefjes , S. Marieke van Ham1* 1 Sanquin Research and Landsteiner Laboratory, Department of Immunopathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 2 Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands Abstract 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 BCR- ligation 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 cross- presentation 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 response and th