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Lung-resident memory B cells protect against bacterial pneumonia
Kimberly A. Barker, … , Lee J. Quinton, Joseph P. Mizgerd
Kimberly A. Barker, … , Lee J. Quinton, Joseph P. Mizgerd
Published June 1, 2021
Citation Information: J Clin Invest. 2021;131(11):e141810. https://doi.org/10.1172/JCI141810.
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Research Article Immunology Pulmonology

Lung-resident memory B cells protect against bacterial pneumonia

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Abstract

Lung-resident memory B cells (BRM cells) are elicited after influenza infections of mice, but connections to other pathogens and hosts — as well as their functional significance — have yet to be determined. We postulate that BRM cells are core components of lung immunity. To test this, we examined whether lung BRM cells are elicited by the respiratory pathogen pneumococcus, are present in humans, and are important in pneumonia defense. Lungs of mice that had recovered from pneumococcal infections did not contain organized tertiary lymphoid organs, but did have plasma cells and noncirculating memory B cells. The latter expressed distinctive surface markers (including CD69, PD-L2, CD80, and CD73) and were poised to secrete antibodies upon stimulation. Human lungs also contained B cells with a resident memory phenotype. In mice recovered from pneumococcal pneumonia, depletion of PD-L2+ B cells, including lung BRM cells, diminished bacterial clearance and the level of pneumococcus-reactive antibodies in the lung. These data define lung BRM cells as a common feature of pathogen-experienced lungs and provide direct evidence of a role for these cells in pulmonary antibacterial immunity.

Authors

Kimberly A. Barker, Neelou S. Etesami, Anukul T. Shenoy, Emad I. Arafa, Carolina Lyon de Ana, Nicole M.S. Smith, Ian M.C. Martin, Wesley N. Goltry, Alexander M.S. Barron, Jeffrey L. Browning, Hasmeena Kathuria, Anna C. Belkina, Antoine Guillon, Xuemei Zhong, Nicholas A. Crossland, Matthew R. Jones, Lee J. Quinton, Joseph P. Mizgerd

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Figure 6

Lung BRM cells are poised to secrete antibody.

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Lung BRM cells are poised to secrete antibody.
(A) Distribution of naive...
(A) Distribution of naive, IgM+IgD–, and class-switched B cells in experienced lungs and spleens (2-way ANOVA comparing isotypes across compartments, n = 3 for spleen, 5 for lung; *P = 0.0022 vs. spleen, P = 0.0009 vs. IV lung; **P < 0.0001 vs. either compartment). (B) Experienced EV lung IgM–IgD– B cell isotypes. n = 5. Representative flow plots from experienced lungs showing MBC marker expression on IgD– EV B cells (C) and coexpression (D) as quantified in E, where numbers of triple-negative (TN), single-positive (SP), and double- or triple-positive (DP/TP) B cells are shown (2-way ANOVA comparing each marker category between naive and experienced mice, *P < 0.0001). Total IgG ELISpot image (F) and counts (G) of spleen and EV lung B cells after ex vivo culture (Kruskal-Wallis test for each organ, *P = 0.028, **P = 0.0035 for spleen, P = 0.006 for lung). Vertical lines in F separate images within a group obtained from different plates. (H) Pneumococcus-specific antibody levels in ex vivo culture supernatants from F and G (Kruskal-Wallis test for each isotype within each organ, *P = 0.0039 for IgG, P = 0.0064 for IgM). (I) Pneumococcus-specific antibody in experienced BALF at baseline or after Sp3 infection (Mann-Whitney U test for each isotype, n = 15 for baseline, n = 8 for 96 hours; *P = 0.0018, **P = 0.0007, ***P < 0.0001).

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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