# Regulation of B cell function and antibody class switching by c-Rel O-GlcNAcylation

> **NIH NIH R21** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $200,729

## Abstract

Abstract
O-GlcNAcylation is an intracellular posttranslational glycosylation that is greatly
enhanced under hyperglycemic conditions such as diabetes. We found that
hyperglycemia induces O-GlcNAcylation of the transcription factor nuclear factor kappa
B (NF-κB) subunit c-Rel at serine 350. c-Rel is predominantly expressed in T and B cells
and controls cell proliferation, survival, and host defense. We discovered that O-
GlcNAcylation of c-Rel in T cells regulates the induction of a subset of genes that may
exacerbate T cell-mediated autoimmunity. Autoimmune diabetes is also associated with
deregulated B cell function and autoantibody production. Both c-Rel and global O-
GlcNAcylation, have been shown independently, to be essential for the regulation of B
cell function. However, the specific role of c-Rel O-GlcNAcylation in B cells remains
unknown. We hypothesize that c-Rel O-GlcNAcylation is a critical regulator of B cell
survival and function as well as altered antibody class switching and autoantibody
production in type 1 diabetes. Here we propose to study the role of c-Rel O-
GlcNAcylation in B cells by reconstitution of non-O-GlcNAcylatable mutant c-Rel in our
novel c-Rel deficient non-obese diabetic mouse model and cellular systems. This study
will (a) ascertain c-Rel O-GlcNAcylation as a novel mechanism regulating transcription
and autoantibody production in B cells and (b) reveal a long-sought-after specific
molecular drug target for the development of new therapeutics to control autoimmunity in
diabetes. This foundational study will also have broad future translational implications in
O-GlcNAcylation-dependent dysregulation of B cell functions in type 1 and type 2
diabetes as well as obesity, where hyperglycemia is involved as a common factor.

## Key facts

- **NIH application ID:** 9876912
- **Project number:** 5R21AI144264-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Parameswaran Ramakrishnan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,729
- **Award type:** 5
- **Project period:** 2019-02-19 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876912

## Citation

> US National Institutes of Health, RePORTER application 9876912, Regulation of B cell function and antibody class switching by c-Rel O-GlcNAcylation (5R21AI144264-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9876912. Licensed CC0.

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