Center for Fundamental Immunology, Benaroya Research Institute, Seattle, WA, USA.
Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, USA.
Sci Immunol. 2023 Jan 6;8(79):eadd9413. doi: 10.1126/sciimmunol.add9413.
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) 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 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.
长寿且高亲和力的抗体来源于生发中心（GC）的活动，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）信号调节 GC 和抗原特异性抗体反应的幅度。GC B 细胞和滤泡辅助 T 细胞（Tfh）都上调表面 TSLP 受体（TSLPR）的表达，但 TSLPR 的细胞特异性缺失会对 GC 的形成和抗体产生产生不同的影响。T 细胞上的 TSLPR 信号支持保留抗原特异性 B 细胞和 T 细胞分化，而 B 细胞中的 TSLPR 则调节抗原特异性记忆 B 细胞的产生。两种细胞类型中的 TSLPR 都促进干扰素调节因子 4（IRF4）的表达，这对于有效的 GC 活性很重要。总的来说，我们确定了一种以前未被重视的 GC 细胞因子调节剂，并确定了这种信号通路如何在 GC 中差异调节 B 和 T 细胞反应。
