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B cell– and T cell–intrinsic regulation of germinal centers by thymic stromal lymphopoietin signaling
Science Immunology ( IF 24.8 ) Pub Date : 2023-01-20 , DOI: 10.1126/sciimmunol.add9413
Phillip P Domeier 1 , Ziaur S M Rahman 2 , Steven F Ziegler 1
Affiliation  

Long-lived and high-affinity antibodies are derived from germinal center (GC) activity, but the cytokines that regulate GC function are still being identified. Here, we show that thymic stromal lymphopoietin (TSLP) signaling regulates the GC and the magnitude of antigen-specific antibody responses. Both GC B cells and T follicular helper (T FH ) cells up-regulate the expression of surface TSLP receptor (TSLPR), but cell-specific loss of TSLPR results in distinct effects on GC formation and antibody production. TSLPR signaling on T cells supports the retention of antigen-specific B cells and T FH differentiation, whereas TSLPR in B cells regulates the generation of antigen-specific memory B cells. TSLPR in both cell types promotes interferon regulatory factor 4 (IRF4) expression, which is important for efficient GC activity. Overall, we identified a previously unappreciated cytokine regulator of GCs and identified how this signaling pathway differentially regulates B and T cell responses in the GC.

中文翻译:

胸腺基质淋巴细胞生成素信号传导对生发中心的 B 细胞和 T 细胞内在调节

长寿命和高亲和力的抗体源自生发中心 (GC) 活性,但调节 GC 功能的细胞因子仍在鉴定中。在这里,我们表明胸腺基质淋巴细胞生成素 (TSLP) 信号传导调节 GC 和抗原特异性抗体反应的强度。GC B 细胞和滤泡辅助 T 细胞(T跳频) 细胞上调表面 TSLP 受体 (TSLPR) 的表达,但 TSLPR 的细胞特异性缺失会对 GC 形成和抗体产生产生明显影响。T 细胞上的 TSLPR 信号传导支持抗原特异性 B 细胞和 T 细胞的保留跳频分化,而 B 细胞中的 TSLPR 调节抗原特异性记忆 B 细胞的生成。两种细胞类型中的 TSLPR 都会促进干扰素调节因子 4 (IRF4) 的表达,这对于高效的 GC 活性非常重要。总体而言,我们发现了一种以前未被重视的 GC 细胞因子调节剂,并确定了该信号通路如何差异调节 GC 中的 B 和 T 细胞反应。
更新日期:2023-01-20
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