# Determining the role of NLRP3 on the placement and protective potential of CD73+ BRMs post influenza infection

> **NIH NIH R21** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $222,750

## Abstract

Project Summary
Little is known about antigen (Ag) specific memory B (BMEM) cells, in the context of a public health relevant
pathogen. Our studies clearly resolve the subsets of non-circulating, influenza specific, resident memory B
cells (BRM) in the lung. BRM establishment relied on early CD40 signaling and maintained a CD73
(ectoenzyme)+ and CD73- population, whereas the lymph node (LN) showed a decline in the CD73-
population. This raised the question of the inherent differences in formation and function of CD73+ and CD73-
BRMs. CD73 is a marker of germinal center (GC) emigrants in the LN and memory cells in the LN reside in
niches close to macrophages that capture and transfer antigen and T cells which can provide help; therefore,
we hypothesized that the CD73+BRMs will home to areas of organized lymphoid structures in the lung and be
dependent on T cell help. Our RNASeq data shows NLRP3 (NOD-like receptor protein 3), an innate danger
sensing complex, to be the most upregulated gene in CD73+BRMs. To our knowledge NLRP3 activity is not
associated with B cell differentiation, which makes this finding novel and may inaugurate studies into innate
like functions in B cells during adaptive responses. NLRP3 activity produces interleukin B (IL-1B) and IL-1B is
a well-known up regulator of interleukin 6 (IL-6), which promotes GCs and plasma cell differentiation. As our
CD73+BRMs may have higher NLRP3 expression, we hypothesize that NLRP3 will be active during recall and
produce GCs and ASCs, while the CD73-BRMs may be sentinels in the lung which spontaneously convert to
ASCs, in response to the returning virus.
To test these hypotheses, we ask the following: 1) Are CD73+ and CD73- BRM cells dependent on GCs? If
so, GC-specific blockade should reduce CD73+ BRMs in the lung and produce low affinity BCRs. 2) Do CD73+
BRMs preferentially reside in iBALT? If so, using histology, we should observe them congregating in the
iBALT while the CD73-BRMs are scattered in the parenchyma. 3) Do CD73+ and CD73- BRM cells respond
differently in functional assays? We will answer this question by performing in vitro assays for BRM
differentiation to ASCs, using cytokine cocktails and sorted T cells. 4) Does the NLRP3 complex become
activated in BRMs upon viral challenge? If so, using NLRP3 inflammasome reporter mice, we expect that
CD73+ BRM cells, but not CD73- BRM cells to increase NLRP3 activity. 5) Does NLRP3 regulate the
formation or function of BRMs? If so, B cell specific NLRP3 deficiency should alter the proportions of
CD73+ and CD73-BRMs and their protective function with observable differences in morbidity and mortality.
The findings from this study despite the outcome will be extremely important to allow for the resolution of a
target population and potential molecular targets for an effective vaccine design.

## Key facts

- **NIH application ID:** 9876793
- **Project number:** 1R21AI149271-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** S Rameeza Allie
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $222,750
- **Award type:** 1
- **Project period:** 2020-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876793

## Citation

> US National Institutes of Health, RePORTER application 9876793, Determining the role of NLRP3 on the placement and protective potential of CD73+ BRMs post influenza infection (1R21AI149271-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9876793. Licensed CC0.

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