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

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 4

Lung B cells in experienced mice are resident.

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Lung B cells in experienced mice are resident. (A) Representative flow c...
(A) Representative flow cytometry plots showing expression of CD69, CD11a, CD62L, and CD44 on IV and EV IgD– lung B cells in experienced mice. (B) Percentage of CD69+ of EV IgD– B cells in the exposed left lung lobe and control right lung lobes of naive and experienced mice (1-way ANOVA, *P = 0.0054, **P = 0.0021, ***P < 0.0001). (C) Median fluorescence intensity (MFI) of CD11a on EV IgD– B cells in the exposed left lung lobe and control right lung lobes of naive and experienced mice (1-way ANOVA, *P = 0.0047, **P = 0.0017, ***P < 0.0001). (D) Fold change in EV IgD– lung B cells between saline-treated and experienced mice in the exposed left lung lobe and unexposed control right lobe. Each dot represents the average fold change in 1 experiment including at least 3 naive and 3 experienced mice (Mann-Whitney U test, *P = 0.036). (E) Binding of a fluorescent anti-CD20 antibody to lung B cells from mice treated 2 weeks previously with isotype control IgG or anti-CD20 (5D2 clone). FMO, fluorescence minus one. Representative flow cytometry plots (F) and quantification CD19+ cells (G) in lung compartments 4 days or 2 weeks after anti-CD20 or IgG treatment of experienced mice (Kruskal-Wallis test, *P = 0.002).