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Within 10 seconds of exposure to the CXCR5 ligand CXCL13, three-dimensional lamellar-like pseudopods and F-actin\u2013rich ridges appeared. The transient F-actin increase depended on G\u03b1\n            <jats:sub>i2\/3<\/jats:sub>\n            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\n            <jats:italic>Wnk1<\/jats:italic>\n            , 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.\n          <\/jats:p>","DOI":"10.1126\/scisignal.ade1119","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T17:58:40Z","timestamp":1724781520000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["Chemokine-mediated F-actin dynamics, polarity, and migration in B lymphocytes depend on WNK1 signaling"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4498-4382","authenticated-orcid":true,"given":"Il-Young","family":"Hwang","sequence":"first","affiliation":[{"name":"B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8943-5771","authenticated-orcid":true,"given":"Ji Sung","family":"Kim","sequence":"additional","affiliation":[{"name":"B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen A.","family":"Harrison","sequence":"additional","affiliation":[{"name":"B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7819-5333","authenticated-orcid":true,"given":"Chung","family":"Park","sequence":"additional","affiliation":[{"name":"B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong Shan","family":"Shi","sequence":"additional","affiliation":[{"name":"B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-159X","authenticated-orcid":true,"given":"John H.","family":"Kehrl","sequence":"additional","affiliation":[{"name":"B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.24.8643"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.129.4.1605"},{"key":"e_1_3_2_4_2","first-page":"143","article-title":"Regulation of neutrophil motility and adhesion by intracellular calcium transients","volume":"19","author":"Hendey B.","year":"1993","unstructured":"B. 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