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

• Published in: Cell reports (Cambridge) 2024-07, Vol.43 (7), p.114426-114426, Article 114426
• Main Authors: Tsai, Chen-Yu, Oo, Myo, Peh, Jih Hou, Yeo, Benjamin C.M., Aptekmann, Ariel, Lee, Bernett, Liu, Joe J.J., Tsao, Wen-Shan, Dick, Thomas, Fink, Katja, Gengenbacher, Martin
• Format: Article
• Language: English
• Subjects: age-associated B cells; Animals; B cells; B-Lymphocyte Subsets - immunology; B-Lymphocytes - immunology; Cytokines - metabolism; Female; Humans; immune landscape; Immunity, Cellular; immunophenotype; Lung - immunology; Lung - microbiology; Lung - pathology; marginal zone B cells; memory-like B cells; Mice; Mice, Inbred C57BL; multiple cytokine production; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; regulatory role; Spleen - immunology; Spleen - microbiology; Tuberculosis - immunology; Tuberculosis - microbiology; unconventional B cells
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114426

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.