Know Your ABCs: Discovery, Differentiation, and Targeting of T-Bet+ B Cells

IF 7.5 2区 医学 Q1 IMMUNOLOGY
Gary M. Winslow, Russell Levack
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Abstract

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.

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来源期刊
Immunological Reviews
Immunological Reviews 医学-免疫学
CiteScore
16.20
自引率
1.10%
发文量
118
审稿时长
4-8 weeks
期刊介绍: Immunological Reviews is a specialized journal that focuses on various aspects of immunological research. It encompasses a wide range of topics, such as clinical immunology, experimental immunology, and investigations related to allergy and the immune system. The journal follows a unique approach where each volume is dedicated solely to a specific area of immunological research. However, collectively, these volumes aim to offer an extensive and up-to-date overview of the latest advancements in basic immunology and their practical implications in clinical settings.
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