# Biochemical Mechanisms for Sustained Humoral Immunity

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $623,408

## Abstract

Project summary
Antibody-secreting plasma cells play critical roles in health and disease, yet little is known
about the biochemical mechanisms controlling antibody synthesis and secretion or how
these pathways intersect with pathways controlling cell survival. Furthermore, due to the
high metabolic demands inherent to robust antibody secretion and the tendency for many
plasma cells to persist for decades, pathways restraining apoptosis in plasma cells are
likely to be integrated in unique ways. This project centers on the hypothesis that long-
lived plasma cells in bone marrow obtain requisite signals to maintain antibody secretion
and avoid cell death by sensing extracellular ATP with a purinergic receptor known as
P2rX4. We further hypothesize that eATP is produced locally in the bone marrow for
plasma cells by osteoblastic cells via the gap junction protein known as Panx3. Thus,
consistent with our preliminary data, inhibition of P2rX4 or Panx3 function is predicted to
cause the depletion of long-lived plasma cells and reduce serum antibody titers including
for disease-associated antibodies. To test our hypothesis, we will: 1) Define cell intrinsic
P2rX4-regulated outcomes for newborn and long-lived plasma cells, and 2) Define cell
extrinsic sources and outcomes for eATP/Panx3 regulation of long-lived plasma cells.
These studies will provide unique and needed insights into the specialized survival
mechanisms employed by long-lived plasma cells. This work supports our long-term
objective of developing strategies to effectively and specifically disable or deplete
problematic plasma cells.

## Key facts

- **NIH application ID:** 10794358
- **Project number:** 5R01AI175185-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** David M Allman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $623,408
- **Award type:** 5
- **Project period:** 2023-02-23 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10794358

## Citation

> US National Institutes of Health, RePORTER application 10794358, Biochemical Mechanisms for Sustained Humoral Immunity (5R01AI175185-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10794358. Licensed CC0.

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