Pulmonary innate immunity is required for host defense; however, excessive neutrophil inflammation can cause life-threatening acute lung injury. B lymphocytes can be regulatory, yet little is known about peripheral transitional IgM+ B cells in terms of regulatory properties. Using single-cell RNA sequencing, we discovered eight IgM+ B cell subsets with unique gene regulatory networks in the lung circulation dominated by transitional type 1 B and type 2 B (T2B) cells. Lung intravital confocal microscopy revealed that T2B cells marginate in the pulmonary capillaries via CD49e and require CXCL13 and CXCR5. During lung inflammation, marginated T2B cells dampened excessive neutrophil vascular inflammation via the specialized proresolving molecule lipoxin A4 (LXA4). Exogenous CXCL13 dampened excessive neutrophilic inflammation by increasing marginated B cells, and LXA4 recapitulated neutrophil regulation in B cell–deficient mice during inflammation and fungal pneumonia. Thus, the lung microvasculature is enriched in multiple IgM+ B cell subsets with marginating capillary T2B cells that dampen neutrophil responses.
Marginating transitional B cells modulate neutrophils in the lung during inflammation and pneumonia
Disclosures: The authors declare no competing interests exist.
- Award Id(s): RS-342013
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John Podstawka, Sarthak Sinha, Carlos H. Hiroki, Nicole Sarden, Elise Granton, Elodie Labit, Jung Hwan Kim, Graciela Andonegui, Yuefei Lou, Brendan D. Snarr, Donald C. Sheppard, Nicole L. Rosin, Jeff Biernaskie, Bryan G. Yipp; Marginating transitional B cells modulate neutrophils in the lung during inflammation and pneumonia. J Exp Med 6 September 2021; 218 (9): e20210409. doi: https://doi.org/10.1084/jem.20210409
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