Chapter 4 Phagocytosis of Salmonella by B cells generates an effective cytotoxic T cell response via cross-presentation of Salmonella-antigens

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. Here we show that Salmonella-specific B cells that phagocytose Salmonella upon BCR-ligation are able to activate human CD8+ memory T cells via cross-presentation yielding a Salmonella-specific cytotoxic T cell response. Unlike the DCs, B cell-mediated cross-presentation of Salmonella does not coincide with apoptosis. Thus, B cells are a viable alternative for DC in the activation of the cytotoxic effector arm and the generation of effective adaptive immunity against Salmonella reinfection. 74 Cross-presentation of Salmonella-antigens by B cell