# Plasma Cells in Health and Disease

> **NIH NIH P01** · EMORY UNIVERSITY · 2020 · $1,747,765

## Abstract

OVERVIEW – ABSTRACT
Plasma cells (PC) constitute the effector arm of the humoral immune system and are responsible for serum
and tissue antibodies. PC combine properties of resting, long-lived memory cells and of effector cells endowed
with constitutive antibody production thereby suggesting their regulation by unique molecular programs. PC
protect against new pathogens and maintain long-lasting serological memory against historical pathogens.
Accordingly, PC are at the core of protective responses in infection, vaccination and anti-tumor immunity.
However, PC also induce antibody-mediated diseases including autoimmunity, allergy and transplant rejection.
Indeed, the activation of PC differentiation in response to self-antigens, alloantigens or allergens carries a
major risk by creating undesirable pro-inflammatory responses. This situation is all the more detrimental when
it involves a unique type of PC that may survive for the lifetime of the patient (long lived plasma cells; LLPC).
Accordingly, understanding programs that govern the differentiation and survival of different types of PC and
how these programs are subverted in human diseases is of the utmost importance to enhance protective PC
responses and regulate pathogenic responses. Unfortunately, PC are severely understudied as a cell type and
as mediators of disease. Our ability to address these questions has been hampered by knowledge gaps and
experimental barriers including lack of specific markers for LLPC. We seek to remedy these deficiencies by
using the knowledge we have gained in the understanding of the phenotypic and functional heterogeneity of
human PC (Projects 2-4), and through the use of animal models of PC differentiation and participation in
disease under well-defined T cell-dependent and –independent conditions (Projects 1-2). This PPG will ask
fundamental questions through complementary and synergistic projects that will generate high-density
datasets of transcriptional and epigenetic programs induced under different experimental conditions. These
questions include: 1) Epigenetic regulation of PC differentiation and survival in mice (Projects 1-2) and
humans (Projects 2, 3, 4); 2) Transcriptional and epigenetic modulation of functionally distinct PC populations
by cytokines and cytokine-induced transcriptional factors (Project 2); 3) Mechanisms of human LLPC survival
through adaptation to the bone marrow microenvironment (Project 3); and 4) Mechanisms of generation and
survival of pathogenic autoreactive LLPC in human SLE (Project 4). These questions will be addressed
through the interaction of scientists with significant contributions in relevant areas and a strong track record of
collaborations. All molecular studies will be performed by an Epigenomics, Sequencing, and
Bioinformatics Core to ensure data quality, reproducibility and sharing. An Administrative Core will provide
leadership, administrative, regulatory and financial infrastructure. The knowledge generated wi...

## Key facts

- **NIH application ID:** 10133836
- **Project number:** 3P01AI125180-05S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Ignacio E. Sanz
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,747,765
- **Award type:** 3
- **Project period:** 2020-06-19 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133836

## Citation

> US National Institutes of Health, RePORTER application 10133836, Plasma Cells in Health and Disease (3P01AI125180-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10133836. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*