# Age-Associated B Cells Specialized for Immunity to Pathogens?

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $209,375

## Abstract

SUMMARY: Age-associated B cells: Specialized for Immunity to Pathogens?
With age the generation of T follicular helpers from naive CD4 T cells and germinal center B cells from follicular
B cells, that are both needed for the generation of high affinity antibody (Ab), become compromised. Most current
vaccines for influenza in the elderly are not effective 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. influenza) and newly emerged pathogens (e.g. COVID-19). We noted the generation of an
unusual population of antibody-secreting B cells to live influenza infection in aged mice, that we found is derived
by stimulation of recently described "age-associated B cells" (ABC). One population of influenza-induced ABC
(iABC) are generated independently of CD4 T cell help, but strictly depend on stimulation by pathogen-
associated "danger" signals. Recently we found that when help is available, a GCB-like response can instead
be induced and produce plasma cells. We also found ABC develop in germ-free mice supporting the intrinsic
nature of the age-associated ABC development. Notably, ABC are the predominant naïve B cells that respond
in aged mice.
Here we will define the signals required from antigen and pathogen-recognition and from CD4 help that generate
the two responses. We have developed transfer approaches that allow us to evaluate whether iABC or GCB
derived from ABC or the Ab produced by each in response to by influenza A virus, can provide protection against
lethal virus and can effectively neutralize or otherwise clear infection with influenza. We will also examine ABC
potential in the context of the elderly host. If we find the aged ABC make a strong contribution to immunity in
otherwise compromised aged hosts, it will justify future major efforts to harness ABC to provide improved
vaccines and immunotherapies for the aged.

## Key facts

- **NIH application ID:** 10401919
- **Project number:** 5R21AG068313-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Susan L Swain
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2021-05-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401919

## Citation

> US National Institutes of Health, RePORTER application 10401919, Age-Associated B Cells Specialized for Immunity to Pathogens? (5R21AG068313-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401919. Licensed CC0.

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