# Contribution of c-Maf to regulatory B cells and antibody-secreting cells

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2021 · $194,375

## Abstract

PROJECT SUMMARY
Regulatory B cells are involved in many pathophysiological processes, such as promoting tolerance in
autoimmunity and organ transplantation, but also reducing immune responses to cancer. Overall, many studies
indicate that regulatory B cells, like regulatory T cells, play a crucial role in regulating the immune system in
many circumstances. A growing body of evidence highlights the strong heterogeneity as well as a high
functional plasticity of regulatory B-cell subsets, which challenge a unique and stable definition. However, a
common function of regulatory B cells is to produce the immunoregulatory cytokine IL-10. While significant
attention has been focused on defining the multiple phenotypes of regulatory B cells, there remains a critical
need to understand the molecular triggers of regulatory B-cell functions. In experiments performed with human
blood B cells, we have obtained preliminary data pointing to specific molecular drivers that control the
generation of IL-10-producing regulatory B cells. Among them, we noticed the transcription factor c-MAF, a
factor belonging to the activator protein-1 (AP-1) superfamily and known to modulate cytokine production in T
cells and macrophages. To date, a function of c-MAF in B cells has not been reported. Results from our
analyses suggest that in humans, c-MAF acts as an early regulator of the generation of IL-10-producing B cells
with a plasmablast phenotype. In addition, a recent publication together with publicly available gene
transcription data indicate that c-Maf can bind the Il10 gene promoter in murine B cells and that, among all
mouse B-cell subsets, is most highly transcribed in plasmablasts. The present study aims to use a tissue-
specific gene knock-out mouse model to explore and establish in vivo the role of c-Maf in the generation of
antibody-secreting cells and IL-10-producing plasmablasts. Specifically, we propose to use established c-Maf-
floxed mice and CD19-Cre mice to generate B-cell conditional c-Maf knock-out mice to test the following: 1) the
function of c-Maf in the steady-state development of plasmablasts and the generation of antibody-secreting
plasmablasts and plasma cells after immunization; and 2) the contribution of c-Maf to the generation of IL-10-
producing regulatory B cells and plasmablasts. Furthermore, these studies will use a Salmonella infection
model to test whether c-Maf contributes to the development of functional regulatory B cells that reduce critical
immune responses. The proposed studies are significant because they are the first to investigate the role of c-
Maf in B-cell biology and because they will lead to a better understanding of the molecular processes
regulating, on one side, the development of plasmablasts and humoral immunity, and on the other, the
generation of regulatory B cells that contribute to exacerbated or ineffective immunity.

## Key facts

- **NIH application ID:** 10216794
- **Project number:** 1R21AI156232-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Roberta Pelanda
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,375
- **Award type:** 1
- **Project period:** 2021-01-28 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216794

## Citation

> US National Institutes of Health, RePORTER application 10216794, Contribution of c-Maf to regulatory B cells and antibody-secreting cells (1R21AI156232-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10216794. Licensed CC0.

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