# Epigenetic instruction of memory B cell function and reactivation

> **NIH NIH R01** · EMORY UNIVERSITY · 2023 · $387,022

## Abstract

Project Summary/Abstract
Protective humoral immunity is mediated by both long-lived memory B cells (MBC) and plasma
cells. MBC are uniquely important because they are multipotent and can rapidly diversify their
BCR repertoire compared to both terminally differentiated plasma cells and naïve B cells. MBC
represent a heterogenous population of cells with different subsets primed to either rapidly
generate plasma cells or form secondary germinal centers. Additionally, MBC can arise in
response to a diverse array of stimuli including independently of a germinal center through a
potential extrafollicular pathway. While all MBC seem to have enhanced recall properties, it is
not known how MBC phenotypes are programed in different subsets or what MBC programming
is dependent on GC? Epigenetic mechanisms are heritable programs that act to guide cell fate
decisions and determine potential phenotypes. Given the cell intrinsic nature of MBC
properties, we hypothesize that MBC harbor a distinct epigenetic programming that serves as a
molecular memory of prior states and instructs cell fate decisions and enhanced function during
recall. Recent work from our group has shown that atypical memory B cells, which are
expanded in patients with autoimmune diseases such as Lupus, show an epigenetic signature
of extrafollicular activation pathways. Thus, a full understanding of MBC properties is essential
to design vaccine strategies that maximize MBC potential and develop therapies that target
diseases where MBC are a component. To elucidate the epigenetic mechanisms governing
MBC phenotypes, we propose two aims designed to 1) define the cis-regulatory landscape,
transcription factor networks, and metabolism of influenza specific MBC subsets that are
derived from or independently of a germinal center; and 2) understand how the epigenetic
repressor EZH2 controls the formation of MBC subsets and recall responses. To accomplish
these aims we have established a series epigenetic and transcriptional profiling protocols and
bioinformatic approaches; assembled a series of genetic mouse strains that allow the
conditional deletion of EZH2; and developed an ex vivo MBC assay to fine map the molecular
changes during recall responses. Ultimately our studies will provide an epigenetic road map to
MBC formation and function and a platform that could aid in the manipulation of immune
memory and therapeutic targets for MBC mediated diseases.

## Key facts

- **NIH application ID:** 10529329
- **Project number:** 5R01AI148471-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Christopher D Scharer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $387,022
- **Award type:** 5
- **Project period:** 2019-12-12 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10529329

## Citation

> US National Institutes of Health, RePORTER application 10529329, Epigenetic instruction of memory B cell function and reactivation (5R01AI148471-04). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10529329. Licensed CC0.

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