# How Distinct Age-Associated B Cell Subsets Can Protect the Aged from Influenza

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $586,250

## Abstract

ABSTRACT: How Distinct Age-Associated B Cell Subsets Can Protect the Aged from Influenza. With age,
the generation of T follicular helpers from naive CD4 T cells, and of germinal center B cells from follicular B cells,
both of which are essential for the generation of high affinity antibody (Ab), become highly compromised. Most
current vaccines for influenza in the elderly are ineffective at inducing these critical responses. Thus, the elderly,
though protected by Ab already in place for pathogens encountered earlier in life, are highly susceptible to new
strains of virus (e.g. new yearly variants of influenza) and newly emerged pathogens (e.g. pandemic influenzas,
COVID-19). In aged mice, we noted the generation of an unusual population of Ab-secreting B cells in response
to live influenza infection. We found they are derived from stimulation of recently described "age-associated B
cells" (ABC) rather than conventional naïve follicular B cells. In aged mice influenza-induced ABC (iABC)
responses are generated independently of CD4 T cell help, but are strictly depend on stimulation by pathogen-
associated "danger" signals. Notably, the ABC are the predominant naïve B cells that respond to influenza
infection in aged mice. We find only the IgD ABC subset of naïve ABC, respond, and that IgD ABC include two
subsets, T-bet+/CD11c+ and T-bet-/CD11c-. Here we will determine the potential of each of these to respond to
infection and generate Ab-secreting cells (AbSC), B cell memory and long-lived Ab-secreting cells in the lung
and nasal tissues as well as the spleen, lymph node and bone marrow and define what signals from the influenza
infection are needed. We will determine the contribution of the T-bet and non-T-bet responses to protection from
reinfection. We will compare the ability of live influenza virus, whole inactivated virus and mRNA-LNP vaccine to
generate ABC-derived responses and induce protective immunity, and test if adding infection-associated signals
improves this. These results will give us new insights into this novel age-associated immune pathway and should
provide new indications of how vaccines can be improved to provide more robust protection to the elderly who
currently are highly vulnerable.

## Key facts

- **NIH application ID:** 10979867
- **Project number:** 1R01AI179760-01A1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Susan L Swain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $586,250
- **Award type:** 1
- **Project period:** 2024-08-19 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979867

## Citation

> US National Institutes of Health, RePORTER application 10979867, How Distinct Age-Associated B Cell Subsets Can Protect the Aged from Influenza (1R01AI179760-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10979867. Licensed CC0.

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