Bacteria‐instructed B cells cross‐prime naïve CD8+ T cells triggering effective cytotoxic responses

In addition to triggering humoral responses, conventional B cells have been described in vitro to cross‐present exogenous antigens activating naïve CD8 + T cells. Nevertheless, the way B cells capture these exogenous antigens and the physiological roles of B cell‐mediated cross‐presentation remain poorly explored. Here, we show that B cells capture bacteria by trans‐phagocytosis from previously infected dendritic cells (DC) when they are in close contact. Bacterial encounter “instructs” the B cells to acquire antigen cross‐presentation abilities, in a process that involves autophagy. Bacteria‐instructed B cells, henceforth referred to as BacB cells, rapidly degrade phagocytosed bacteria, process bacterial antigens and cross‐prime naïve CD8 + T cells which differentiate into specific cytotoxic cells that efficiently control bacterial infections. Moreover, a proof‐of‐concept experiment shows that BacB cells that have captured bacteria expressing tumor antigens could be useful as novel cellular immunotherapies against cancer. Synopsis B cells capturing Listeria monocytogenes acquire antigen cross‐presentation abilities in a process that involves autophagy. These bacteria‐instructed B cells (BacB) effectively cross‐prime naïve CD8 + T cells which differentiate into specific cytotoxic cells that efficiently control bacterial infections. Conventional B cells capture bacteria by transphagocytosis. The capture of L. monocytogenes instructs B cells (BacB) to became antigen cross‐presenting cells. BacB capturing bacteria expressing tumor antigens could be useful as novel cellular immunotherapy against cancer. Graphical Abstract B cells capturing Listeria monocytogenes acquire antigen cross‐presentation abilities in a process that involves autophagy. These bacteria‐instructed B cells (BacB) effectively cross‐prime naïve CD8 + T cells which differentiate into specific cytotoxic cells that efficiently control bacterial infections.