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 8

Lung PD-L2+ MBC are required for optimal serotype-independent antipneumococcal lung immunity and local IgG production.

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Lung PD-L2+ MBC are required for optimal serotype-independent antipneumo...
(A) Timeline of treatments in PZTD mice. Representative plots of EV lung B cells in naive and experienced Cre+ mice (B) and in experienced Cre+ mice with or without DT (C). (D) Quantification of PD-L2+ EV B cells in lungs of experienced Cre– and Cre+ mice with or without DT (2-way ANOVA, n = 7 for vehicle-treated Cre–, n = 3 for DT-treated Cre–, n = 8 for vehicle-treated Cre+, and 10 for DT-treated Cre+ mice; *P = 0.029). (E) Weight loss after Sp3 challenge in DT-treated experienced Cre– and Cre+ mice (2-way ANOVA comparing genotypes at each time point, n = 11 per genotype; *P = 0.0093). (F) Ninety-six-hour lung Sp3 burdens in DT-treated experienced Cre– and Cre+ mice (Mann-Whitney U test, *P = 0.0004). Squares, female; circles, male for Cre+ group. One male mouse (identified with an X) died shortly before lung harvest. IL-17 (G) and IFN-γ (H) levels in lung homogenates of DT-treated experienced PZTD mice after 24 or 96 hours of Sp3 infection (no significant differences by Mann-Whitney U tests within each time point). (I) Plasma of mice from F was assessed for Sp3-reactive antibodies via ELISA (no significant differences by Mann-Whitney U test within each isotype). (J) BALF from experienced DT-treated Cre– and Cre+ PZTD mice was collected in a single experiment 96 hours after i.n. Sp3 infection and assessed for Sp3-reactive antibodies via ELISA. Two-way ANOVAs, n = 6 for Cre– mice and n = 4 for Cre+ mice; *P = 0.048. hpi, hours after infection.