Laboratory of Molecular Biology and Immunology, National Institutes of Health, National Institute on Aging, Baltimore, MD, United States.
Laboratory of Genetics & Genomics, National Institutes of Health, National Institute on Aging, Baltimore, MD, United States.
Front Immunol. 2023 Jan 23;14:1067459. doi: 10.3389/fimmu.2023.1067459. eCollection 2023.
The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren's syndrome and Lupus in humans and, germline deletion of the gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for polymorphisms associated with B cell dominated autoimmune diseases in humans.
普遍表达的转录因子 TFII-I 是一种多功能蛋白，在基因调控中具有多种作用。TFII-I 相关的多态性与人类的干燥综合征和狼疮有关，而小鼠中该基因的种系缺失导致胚胎致死。在这里，我们报告了 TFII-I 在 B 淋巴细胞固有特性的动态平衡中的独特作用。在小鼠 B 谱系细胞中缺失 会导致转录组、染色质景观和相关转录因子结合位点发生改变，表现出髓样特征，并与 LPS 诱导的基因表达增强的敏感性相一致。TFII-I 缺陷的 B 细胞也显示出增加的 IgG3 转换，这是一种与炎症相关的表型。这些结果表明 TFII-I 在维持免疫动态平衡中起作用，并为与人类 B 细胞主导的自身免疫性疾病相关的 多态性提供了线索。
