Splenic marginal zone B cells restrict Mycobacterium tuberculosis infection by shaping the cytokine pattern and cell-mediated immunity.

Understanding the role of B cells in tuberculosis (TB) is crucial for developing new TB vaccines. However, the changes in B cell immune landscapes during TB and their functional implications remain incompletely explored. Using high-dimensional flow cytometry to map the immune landscape in response to Mycobacterium tuberculosis (Mtb) infection, our results show an accumulation of marginal zone B (MZB) cells and other unconventional B cell subsets in the lungs and spleen, shaping an unconventional B cell landscape. These MZB cells exhibit activated and memory-like phenotypes, distinguishing their functional profiles from those of conventional B cells. Notably, functional studies show that MZB cells produce multiple cytokines and contribute to systemic protection against TB by shaping cytokine patterns and cell-mediated immunity. These changes in the immune landscape are reversible upon successful TB chemotherapy. Our study suggests that, beyond antibody production, targeting the regulatory function of B cells may be a valuable strategy for TB vaccine development. [Display omitted] • MZB cells accumulate in the lungs and spleen in response to Mtb infection • MZB cells produce multiple cytokines during infection • Splenic MZB cells restrict infection by shaping cytokine patterns • Splenic MZB cells restrict infection by orchestrating cell-mediated immunity Tsai et al. show that marginal zone B cells accumulate in the lungs and spleen in response to Mycobacterium tuberculosis infection, exhibiting activated, memory-like phenotypes and producing multiple cytokines. Splenic marginal zone B cells restrict infection by coordinating the systemic cytokine pattern and cell-mediated immunity. [ABSTRACT FROM AUTHOR]