# Molecular Analysis and Lineage Tracing of Influenza-Specific, Lung-Resident Memory B Cells

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $1,099,708

## Abstract

ABSTRACT
Our recently published data show that memory B cells elicited by influenza infection reside in both lymphoid
tissues and the lung (Allie et al Nat Immunol 2019). Memory B cells in the lung do not recirculate and have
properties, including broad cross-reactivity, that distinguish them from their lymphoid counterparts. We termed
these cells lung-resident memory B cells or BRM cells. Influenza-specific BRM cells rapidly colonize the lung,
where they reside in both the lung tissue and the lung airways for months. Upon challenge infection, lung BRM
cells differentiate in situ and become antibody-secreting cells (ASCs) that contribute to secondary protection.
Our data also show that antigen deposition in the lung is essential for BRM cell formation – perhaps because
BRM cells are generated locally in inducible Bronchus-Associated Lymphoid Tissue (iBALT) or because BRM
precursors generated in lymph nodes need to re-encounter antigen in the lung in order to become resident in
that location. Taken together, these data suggest that BRM cells are an important component of immunity to
influenza, however we have only a rudimentary understanding of where BRM cells come from, how they are
selected, what antigens they react with and how they are recalled (or not) after vaccination or secondary
infection. Our central hypothesis is that BRM cells in the lung are formed from a distinct subset of
responding B cells, are uniquely selected for broad reactivity, and respond exclusively to respiratory antigens.
To test this hypothesis, we will take advantage of single cell methods that allow us to define individual B cells
by a combination of transcriptome (single cell RNseq), BCR clonotype (single cell BCRseq), DNA-barcoded
antibodies to surface markers (CITEseq) and affinity/specificity/cross-reactivity of BCRs cloned and expressed
as recombinant antibodies (single cell cloning). Using these methods to compare populations of influenza-
specific B cells in the lung, draining lymph node, spleen and blood over time and after challenge infection or
vaccination, we will be able to determine how memory B cells in various tissues (particularly the lung) are
related to one another, the depth of their selection, the extent of their cross-reactivity and how they can be
recalled by either vaccination or infection. This information will give us a clear path forward in designing
vaccines that elicit broadly reactive BRM cells that home to the lung and provide long-lived immunity against a
wide variety of influenza subtypes.

## Key facts

- **NIH application ID:** 10140302
- **Project number:** 5R01AI152476-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Troy D Randall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,099,708
- **Award type:** 5
- **Project period:** 2020-04-07 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140302

## Citation

> US National Institutes of Health, RePORTER application 10140302, Molecular Analysis and Lineage Tracing of Influenza-Specific, Lung-Resident Memory B Cells (5R01AI152476-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10140302. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*