调节性 B (Breg) 细胞是一种免疫细胞，在肿瘤微环境中表现出免疫抑制行为。然而，这些 Breg 细胞的分化和调控机制仍有待探索。人鼻咽癌 (NPC) 的单细胞转录组测序分析显示，肿瘤微环境中 B 细胞亚群显着富集，其特征是 EGR1 和 EGR3 高表达。值得注意的是，在缺氧微环境中，这些B细胞诱导MAPK通路激活，随后触发转录因子EGR1和EGR3的激活，进一步调节TGFB1和IL10等免疫抑制因子的表达。在使用缺氧诱导的原代 B 细胞并与癌细胞共移植的移植实验中，观察到肿瘤生长显着增加。机制实验表明，EGR1hi和EGR3 B细胞通过分泌IL16和TNF-α进一步激活Treg细胞的成熟和免疫抑制功能。因此，本研究确定了关键转录因子 EGR1 和 EGR3 作为重要的调节因子，并阐明了缺氧条件下 Breg 细胞的分化。版权所有 © 2024 Elsevier Ltd. 保留所有权利。

Regulatory B (Breg) cells is a type of immune cell that exhibit immunosuppressive behavior within the tumor microenvironment. However, the differentiation and regulatory mechanisms of these Breg cells remain unexplored. Single-cell transcriptome sequencing analysis of human nasopharyngeal carcinoma (NPC) revealed a significant enrichment of B cell subset characterized by high expression of EGR1 and EGR3 in the tumor microenvironment. Notably, in the hypoxic microenvironment, these B cells induce MAPK pathway activation, subsequently triggering the activation of transcription factors EGR1 and EGR3, which further modulate the expression of immunosuppressive factors like TGFB1 and IL10. In transplant experiments using primary B cells induced under hypoxia and co-transplanted with cancer cells, a significant increase in tumor growth was observed. Mechanism experiments demonstrated that EGR1hi and EGR3+ B cells further activate the maturation and immunosuppressive function of Treg cells through the secretion of IL16 and TNF-α. Hence, this study identifies the key transcription factors EGR1 and EGR3 as essential regulators and elucidates the differentiation of Breg cells under hypoxic conditions.Copyright © 2024 Elsevier Ltd. All rights reserved.