4.7 Article

Bacteria-instructed B cells cross-prime naive CD8+ T cells triggering effective cytotoxic responses

Journal

EMBO REPORTS
Volume 24, Issue 7, Pages -

Publisher

WILEY
DOI: 10.15252/embr.202256131

Keywords

B cell-mediated antigen cross-presentation; cancer immunotherapy; cellular therapy; Listeria monocytogenes; transphagocytosis

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Research shows that B cells capture bacteria from infected dendritic cells through trans-phagocytosis, and this process activates CD8(+) T cells to regulate bacterial infections. Additionally, it is demonstrated that B cells that have captured bacteria expressing tumor antigens may be utilized as novel cellular immunotherapies against cancer.
In addition to triggering humoral responses, conventional B cells have been described in vitro to cross-present exogenous antigens activating naive 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 naive 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.

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