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<p>Regulatory B cells (Bregs) cooperate with FOXP3⁺ regulatory T cells (Tregs) to maintain immune tolerance. Among diverse Breg subsets, IL-10⁺ Bregs are the best-defined mediators of suppression across autoimmunity and cancer. We synthesize evidence that histone deacetylases (HDACs) are the central epigenetic switch coupling cytokine and checkpoint signals to the Il10 locus, thereby programming Breg identity and stabilizing immunosuppression. Mechanistically, Blimp-1, STAT3, and c-Maf integrate environmental cues (e.g., LPS, IL-21, TIM-1 ligation) with HDAC-directed chromatin accessibility, while BACH2 and HDAC3 restrain Prdm1 to gate plasmablast-like Breg differentiation. We outline how this HDAC–IL-10 module coordinates Breg–Treg crosstalk (CD40/CD40L, PD-1/PD-L1, TIGIT, adenosinergic CD39/CD73) to suppress Th1/Th17 effectors. Disease context dictates outcome: Breg deficits fuel autoimmunity, whereas Breg expansion/reprogramming in tumors dampens cytotoxic immunity (PD-L1⁺, VISTA⁺, IL-35⁺ Bregs). We propose a framework for precision epigenetic modulation: enhancing HDAC-sensitive Breg programs to restore tolerance in autoimmunity, and disrupting tumor-skewed Breg circuits (PD-L1/VISTA, IL-35/STAT3, adenosine metabolism) to improve cancer immunotherapy. This perspective unifies Breg heterogeneity under a tractable axis—HDAC-tuned IL-10 chromatin—and highlights clinically actionable levers at the interface of epigenetics and immune regulation.</p>

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Regulatory B Cells at the Crossroads of Epigenetic Control and Immune Homeostasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月8日

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  • Duminduni Hewa Angappulige,
  • Darby J. Ballard,
  • Christina James Thomas,
  • Shan Xu,
  • Xinlei Guo,
  • Yashvi Bhavin Gandhi,
  • Sushim Mishra,
  • Paul de Figueiredo,
  • Jianxun Song

摘要

Regulatory B cells (Bregs) cooperate with FOXP3⁺ regulatory T cells (Tregs) to maintain immune tolerance. Among diverse Breg subsets, IL-10⁺ Bregs are the best-defined mediators of suppression across autoimmunity and cancer. We synthesize evidence that histone deacetylases (HDACs) are the central epigenetic switch coupling cytokine and checkpoint signals to the Il10 locus, thereby programming Breg identity and stabilizing immunosuppression. Mechanistically, Blimp-1, STAT3, and c-Maf integrate environmental cues (e.g., LPS, IL-21, TIM-1 ligation) with HDAC-directed chromatin accessibility, while BACH2 and HDAC3 restrain Prdm1 to gate plasmablast-like Breg differentiation. We outline how this HDAC–IL-10 module coordinates Breg–Treg crosstalk (CD40/CD40L, PD-1/PD-L1, TIGIT, adenosinergic CD39/CD73) to suppress Th1/Th17 effectors. Disease context dictates outcome: Breg deficits fuel autoimmunity, whereas Breg expansion/reprogramming in tumors dampens cytotoxic immunity (PD-L1⁺, VISTA⁺, IL-35⁺ Bregs). We propose a framework for precision epigenetic modulation: enhancing HDAC-sensitive Breg programs to restore tolerance in autoimmunity, and disrupting tumor-skewed Breg circuits (PD-L1/VISTA, IL-35/STAT3, adenosine metabolism) to improve cancer immunotherapy. This perspective unifies Breg heterogeneity under a tractable axis—HDAC-tuned IL-10 chromatin—and highlights clinically actionable levers at the interface of epigenetics and immune regulation.