BAFF promotes follicular helper T cell development and germinal center formation through BR3 signal.

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL JCI insight Pub Date : 2024-11-08 DOI:10.1172/jci.insight.183400
Ye Chen, Maogen Chen, Yu Liu, Qiang Li, Youqiu Xue, Liu Liu, Rongzhen Liang, Yiding Xiong, Jun Zhao, Jingrong Chen, Weidong Lin, Julie Wang, Yun Feng Pan, William Stohl, Song Guo Zheng
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Abstract

T follicular helper (Tfh) cells represent an important subset of CD4+ T cells that is crucial to the maturation and differentiation of B cells and the production of high-affinity antibodies. Because B cell activating-factor (BAFF), a vital B cell survival factor, is also crucial to B cell maturation and differentiation, we assessed the effects of BAFF on Tfh cell development and function. We demonstrated that deficiency of BAFF, but not of APRIL, markedly inhibited Tfh cell development, germinal center (GC) formation, and antigen-specific antibody production. The promoting effect of BAFF on Tfh cell development was dependent on expression of BR3 on T cells, and its promoting effect on GC formation was dependent on expression of BR3 on both T cells and B cells. BAFF directly promoted expression of the Tfh cell-characteristic genes via NF-κB signaling. This effect did need BR3 expression. Thus, BAFF not only has direct effects on B cells, but it also has direct effects on Tfh cell differentiation via engagement of BR3, which collectively promoted GC formation and production of high-affinity antibodies. This dual effect of BAFF on B cells and Tfh cells may help explain the clinical utility of BAFF antagonists in the management of certain autoimmune diseases.

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BAFF 通过 BR3 信号促进滤泡辅助性 T 细胞的发育和生殖中心的形成。
T 滤泡辅助细胞(Tfh)是 CD4+ T 细胞的一个重要亚群,对 B 细胞的成熟和分化以及高亲和力抗体的产生至关重要。BAFF是一种重要的B细胞存活因子,对B细胞的成熟和分化也至关重要,因此我们评估了BAFF对Tfh细胞发育和功能的影响。我们证明,缺乏 BAFF(而非 APRIL)会明显抑制 Tfh 细胞的发育、生殖中心(GC)的形成和抗原特异性抗体的产生。BAFF对Tfh细胞发育的促进作用依赖于T细胞上BR3的表达,而其对GC形成的促进作用依赖于T细胞和B细胞上BR3的表达。BAFF 通过 NF-κB 信号直接促进 Tfh 细胞特征基因的表达。这种作用需要 BR3 的表达。因此,BAFF 不仅对 B 细胞有直接作用,而且还通过 BR3 的参与对 Tfh 细胞的分化有直接作用,从而共同促进 GC 的形成和高亲和性抗体的产生。BAFF 对 B 细胞和 Tfh 细胞的这种双重作用可能有助于解释 BAFF 拮抗剂在治疗某些自身免疫性疾病方面的临床用途。
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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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