# Regulation of the follicular T-cell response to autoimmunity

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2021 · $429,521

## Abstract

PROJECT SUMMARY
 The generation of high-affinity antibodies and avoidance of autoimmune responses after
microbial infection or vaccination requires precise control of the germinal center (GC) reaction
by follicular T-cell subsets. Follicular helper CD4+ T (TFH) cells induce GC formation and help
GC B cells to produce protective antibody responses to invading pathogens. FoxP3+ follicular
regulatory T (TFR) cells inhibit TFH-driven GC responses and prevent emergence of auto-reactive
B-cells and autoantibody formation. A key element in stable differentiation of both TFH and TFR is
expression of the antagonistic Bcl6–Blimp1 pair of transcription factors (TF). Our recent studies
of TFH differentiation have revealed that (a) ICOS-dependent binding of OPN-i to the Bcl6-RD2
domain promotes association of Bcl6 with the Mi-2β nucleosome remodeling and histone-
deacetylase complex (Mi2β–NuRD) and (b) this Bcl6-containing complex is essential for
efficient repression of Blimp1, TFH lineage stability and repression of alternative TH fates. We
examine the molecular basis of this process in SA1. Analysis of ICOS+ TFR has also revealed an
association between OPN-i, Bcl6, and components of the Mi2β-NuRD complex. We test the
hypothesis that OPN-i-dependent formation of the Bcl6–Mi-2β-NuRD complex regulates a
common genetic program expressed by TFR and TFH cells. This will entail identification of shared
genetic loci that are co-occupied by Bcl6 and Mi2-β-NuRD according to Bio-ChIP-Seq and
“ChIP-reChIP” analyses (SA2). Finally, we define the mechanism that allows co-expression of
the antagonistic Bcl6–Blimp1 transcription factors in TFR and the contribution of Blimp1 to stable
development and function of TFR cells is addressed in SA3. These studies should provide new
insight into the molecular control of TFH/TFR differentiation and establish a foothold for new
therapeutic approaches to autoimmune disease.

## Key facts

- **NIH application ID:** 10066305
- **Project number:** 5R01AI048125-14
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** HARVEY CANTOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $429,521
- **Award type:** 5
- **Project period:** 2000-04-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066305

## Citation

> US National Institutes of Health, RePORTER application 10066305, Regulation of the follicular T-cell response to autoimmunity (5R01AI048125-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10066305. Licensed CC0.

---

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