# The Influence of Aging on Plasma Cell Function and Bone Marrow Competition

> **NIH NIH F31** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $48,974

## Abstract

Abstract:
Aging represents a prominent risk factor for infection-related mortality. This heightened susceptibility to
infection is closely associated to the attenuation of both strength and durability of humoral responses in elderly
humans and mice following vaccination. Extensive clinical and fundamental aging research point to a few
mechanisms attributing to immune dysfunction, yet antibody titers are reduced and tend to decay faster.
Plasma cells (PCs) are rare, radiation resistant, terminally differentiated B cells responsible for maintaining
long lasting serological memory. With aging, PCs accumulate, however it does not correlate to enhanced
protection. Thus, PCs may play a detrimental role during vaccine responses in the elderly. Within the bone
marrow (BM) niche, PCs demonstrate a ‘stop and go’ motility pattern, allowing them to freely navigate in the
BM and assemble into or disassemble from clusters. A subset of PCs known for their ability to survive for years
in humans and mice are recognized as long-lived PCs (LLPCs). Intravital imaging of mouse BM LLPCs reveals
that they are arrested in survival clusters, which we have found are not formed in APRIL-deficient mice, a
critical cytokine involved in PC longevity. With aging, human-derived BM morphonuclear cells express,
produce, and secrete reduced levels of APRIL. Moreover, the increase in TNFα and other pro-inflammatory
cytokines with aging, or inflamm-aging, may contribute to increased pressure for survival of newly generated
PCs but not LLPCs after vaccination. While PCs accumulate with age, preliminary data from our lab indicates
that LLPCs are enriched in the PC pool of elderly mice. Thus, my overall hypothesis is that, with aging, the
accumulation of LLPCs dysregulates humoral immunity through competition against nascent PCs. I
aim to test this hypothesis in numerous and robust ways. By using adult (3–5 month old) and elderly (20-24
month old) C57B6/J mice, unique genetic tools targeting PCs, 2-photon intravital imaging, spectral flow
cytometry, and high through-put sequencing, I will be able to enumerate the accumulation of BM LLPCs and
comprehensively demonstrate competition between pre-existing PCs and nascent PCs. Ultimately, this study
proposes a novel competition model and the first ever single cell-RNA sequencing library on aging PCs. The
outcomes of this study can lead to an improvement in current vaccinations for elderly individuals or tailored
vaccines for this demographic.

## Key facts

- **NIH application ID:** 10993265
- **Project number:** 1F31AI186234-01
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Luis Jose Ovando
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993265

## Citation

> US National Institutes of Health, RePORTER application 10993265, The Influence of Aging on Plasma Cell Function and Bone Marrow Competition (1F31AI186234-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10993265. Licensed CC0.

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