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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 5

Human lungs are enriched for B cells bearing a resident memory phenotype.

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Human lungs are enriched for B cells bearing a resident memory phenotype...
(A) Normal tissue from wedge resection or biopsy samples from humans with lung cancer were collagenase digested and analyzed via flow cytometry using the gating scheme shown. (B–F) Various cell surface phenotypes of B and T cells in the human lung digests. (B) Percentage of CD4+ and CD19+ cells among live, single cells (Mann-Whitney U test, *P = 0.0023). (C) Percentage of CD27+ cells among all CD19+ cells and among naive (CD19+IgD+) B cells (Mann-Whitney U test, *P = 0.0025). (D) Percentage of CD69+ cells among CD4+ cells, memory B cells (CD19+CD27+), and naive B cells (Kruskal-Wallis test, *P = 0.021, **P = 0.049). (E) Percentage of memory B cells that are class switched (Class sw.) and percentage that are IgM+ (Mann-Whitney U test, *P = 0.0079). (F) Percentage of resident memory B cells (CD27+CD69+CD19+) negative for the B cell activation marker CD83 and for CD38.

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

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