# Protective lung memory B cell functions and dynamics during respiratory infection

> **NIH NIH F30** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $51,752

## Abstract

Project Summary/Abstract
The immune cells of the human lung are exposed to a variety of environmental microbes and allergens with
each inhalation. As a result of these constant exposures in the setting of the lung, their properties and
functions compared to analogous immune cells in other parts of the body are evidently unique, but still poorly
understood. We have successfully used a Streptococcus pneumoniae (Sp) bacterial infection model in mice to
show that lung resident memory CD4+ T cells are established locally and contribute to heterotypic immunity
against related, but non-identical infections after priming with heterologous Sp exposures. Using this model, we
recently discovered that IgM+ and class-switched resident memory B cells are also established in response to
Sp infections in a manner that is independent of tertiary lymphoid structure induction. Although we observed
that the presence of the PD-L2+ memory B cell subset is required for maximum heterotypic protection, the
mechanism by which they convey protection has not been determined. Further, tissue resident memory B cells
have only been demonstrated previously in virally infected lungs containing tertiary lymphoid structures, which
were thought to be crucial to the lung memory B cell pool. Despite the lack of organized lymphoid tissue in the
Sp infection model, our preliminary data reveal that a population of lung B cells bearing markers associated
with germinal centers precedes the development of protective PD-L2+ memory B cells, coinciding with a
transient elevation in PD-1 expression on CD4+ T cells and the follicular organizational chemokine, CXCL13 in
the lung. To elucidate the mechanisms underlying the establishment and function of protective lung memory B
cells in a model lacking ectopic lymphoid tissues, we will pursue the hypotheses described in the following
aims: 1) that lung resident memory PD-L2+ B cells confer heterotypic immunity against respiratory infection via
secretion of cross-reactive antibodies, and 2) that lung B cells require CD4+ T cells for the optimal generation
of protective lung PD-L2+ B resident memory cells. Even prior to the SARS-CoV-2 global health crisis
beginning in late 2019, lower respiratory infections have been a leading cause of morbidity and mortality
worldwide. Advancing our understanding of protective lung B cell dynamics and function in host defense
against respiratory infection will be essential for the rational design of therapeutics and preventative strategies
that will stimulate protective local B cell establishment and activity.

## Key facts

- **NIH application ID:** 10441152
- **Project number:** 5F30HL158109-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Neelou Etesami
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2021-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10441152

## Citation

> US National Institutes of Health, RePORTER application 10441152, Protective lung memory B cell functions and dynamics during respiratory infection (5F30HL158109-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10441152. Licensed CC0.

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