STING 通过与 PI3K 偶联来调节 BCR 激活过程中的肌动蛋白重组。

STING couples with PI3K to regulate actin reorganization during BCR activation.

机构信息

Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Sci Adv. 2020 Apr 22;6(17):eaax9455. doi: 10.1126/sciadv.aax9455. eCollection 2020 Apr.

The adaptor protein, STING (stimulator of interferon genes), has been rarely studied in adaptive immunity. We used KO mice and a patient's mutated cells to study the effect of STING deficiency on B cell development, differentiation, and BCR signaling. We found that STING deficiency promotes the differentiation of marginal zone B cells. STING is involved in BCR activation and negatively regulates the activation of CD19 and Btk but positively regulates the activation of SHIP. The activation of WASP and accumulation of F-actin were enhanced in KO B cells upon BCR stimulation. Mechanistically, STING uses PI3K mediated by the CD19-Btk axis as a central hub for controlling the actin remodeling that, in turn, offers feedback to BCR signaling. Overall, our study provides a mechanism of how STING regulates BCR signaling via feedback from actin reorganization, which contributes to positive regulation of STING on the humoral immune response.

衔接蛋白 STING（干扰素基因刺激蛋白）在适应性免疫中研究较少。我们使用 KO 小鼠和患者突变的细胞来研究 STING 缺陷对 B 细胞发育、分化和 BCR 信号的影响。我们发现 STING 缺陷促进边缘区 B 细胞的分化。STING 参与 BCR 激活，负调节 CD19 和 Btk 的激活，但正调节 SHIP 的激活。在 BCR 刺激下，KO B 细胞中的 WASP 激活和 F-actin 积累增强。在机制上，STING 使用 CD19-Btk 轴介导的 PI3K 作为控制肌动蛋白重塑的中央枢纽，肌动蛋白重塑反过来又为 BCR 信号提供反馈。总的来说，我们的研究提供了一种机制，即 STING 如何通过肌动蛋白重组的反馈来调节 BCR 信号，这有助于 STING 对体液免疫反应的正调节。