配体接合的趋化因子受体触发异源三聚体 Gαi 蛋白中的核苷酸交换，从而刺激细胞骨架重组和细胞极性变化。为了更好地了解导致这些细胞变化的信号传导事件，我们重点研究了小鼠脾 B 细胞中趋化因子受体 CXCR5 参与后 F-肌动蛋白动力学的早期变化。在暴露于 CXCR5 配体 CXCL13 的 10 秒内，出现了三维层状伪足和富含 F-肌动蛋白的脊。 F-肌动蛋白的瞬时增加取决于 Gαi2/3 信号传导、PI3K/AKT 通路、ERK 激活、磷脂酶 C 活性和 Dock2（胞质分裂 2 的贡献者）介导的 Rac1/2 激活。免疫印迹分析确定激酶 WNK1（不含赖氨酸激酶 1）是潜在的早期 AKT 效应子。用特定的 WNK 抑制剂处理 B 细胞会破坏 F-肌动蛋白动力学，并损害 B 细胞极性、运动性和趋化性。通过对 Wnk1 进行 CRISPR-Cas9 基因编辑，在小鼠 B 细胞系中模拟了这些变化，这也表明 WNK1 有助于 B 细胞增殖。单剂量的 WNK 抑制剂可暂时降低活体小鼠淋巴结中的 B 细胞运动性和极性。这些结果表明 WNK1 信号传导维持 B 细胞对 CXCL13 的反应性，并表明对参与癌症进展和血压调节的 WNK1 进行药理抑制可能会影响体液免疫。

Ligand-engaged chemokine receptors trigger nucleotide exchange in heterotrimeric Gαi proteins, which stimulates cytoskeletal reorganization and cell polarity changes. To better understand the signaling events responsible for these cellular changes, we focused on early changes in F-actin dynamics after engagement of the chemokine receptor CXCR5 in murine splenic B cells. Within 10 seconds of exposure to the CXCR5 ligand CXCL13, three-dimensional lamellar-like pseudopods and F-actin-rich ridges appeared. The transient F-actin increase depended on Gαi2/3 signaling, the PI3K/AKT pathway, ERK activation, phospholipase C activity, and Rac1/2 activation mediated by Dock2 (dedicator of cytokinesis 2). Immunoblot analyses identified the kinase WNK1 (with no lysine kinase 1) as a potential early AKT effector. Treating B cells with specific WNK inhibitors disrupted F-actin dynamics and impaired B cell polarity, motility, and chemotaxis. These changes were mimicked in a murine B cell line by CRISPR-Cas9 gene editing of Wnk1, which also suggested that WNK1 contributed to B cell proliferation. Administration of a single dose of a WNK inhibitor transiently reduced B cell motility and polarity in the lymph nodes of live mice. These results indicate that WNK1 signaling maintains B cell responsiveness to CXCL13 and suggest that pharmacological inhibition of WNK1, which is involved in cancer progression and blood pressure regulation, may affect humoral immunity.