Winslow Gary M, Levack Russell
Department of Microbiology and Immunology, Upstate Medical University, Syracuse, New York, USA.
Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Immunol Rev. 2025 Mar;330(1):e13440. doi: 10.1111/imr.13440.
Since their first description in 2008, T-bet+ B cells have emerged as a clinically important B cell subset. Now commonly known as ABCs (Age-associated B Cells), they are uniquely characterized by their expression of the transcription factor T-bet. Indeed, this singular factor defines this B cell subset. This review will describe the discovery of T-bet+ B cells, their role in bacterial infection as T cell-independent (TI) plasmablasts, as well as long-term follicular helper T cell-dependent (TD) IgM+ and switched memory cells (i.e., T-bet+ ABCs), and later discoveries of their role(s) in diverse immunological responses. These studies highlight a critical, although limited, role of T-bet in IgG2a class switching, a function central to the cells' role in immunity and autoimmunity. Given their association with autoimmunity, pharmacological targeting is an attractive strategy for reducing or eliminating the B cells. T-bet+ ABCs express a number of characteristic cell surface markers, including CD11c, CD11b, CD73, and the adenosine 2a receptor (A2aR). Accordingly, A2aR agonist administration effectively targeted T-bet+ ABCs in vivo. Moreover, agonist treatment of lupus-prone mice reduced autoantibodies and disease symptoms. This latter work highlights the potential therapeutic use of adenosine agonists for treating autoimmune diseases involving T-bet+ ABCs.
自2008年首次被描述以来，T-bet+ B细胞已成为临床上重要的B细胞亚群。现在通常被称为ABCs（年龄相关B细胞），它们的独特特征是转录因子T-bet的表达。事实上，这个单一因子定义了这个B细胞亚群。本综述将描述T-bet+ B细胞的发现、它们作为非T细胞依赖性（TI）浆母细胞在细菌感染中的作用，以及长期滤泡辅助性T细胞依赖性（TD）IgM+和转换记忆细胞（即T-bet+ ABCs），以及后来发现它们在多种免疫反应中的作用。这些研究突出了T-bet在IgG2a类别转换中的关键作用，尽管有限，但这一功能对于细胞在免疫和自身免疫中的作用至关重要。鉴于它们与自身免疫的关联，药物靶向是减少或消除这些B细胞的一种有吸引力的策略。T-bet+ ABCs表达多种特征性细胞表面标志物，包括CD11c、CD11b、CD73和腺苷2a受体（A2aR）。因此，给予A2aR激动剂可在体内有效靶向T-bet+ ABCs。此外，对易患狼疮的小鼠进行激动剂治疗可减少自身抗体和疾病症状。后一项工作突出了腺苷激动剂在治疗涉及T-bet+ ABCs的自身免疫性疾病中的潜在治疗用途。
