{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:50:45Z","timestamp":1791935445490,"version":"4.3.4"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Naive B cells use the chemokine receptor CXCR5 to enter B cell follicles, where they scan CXCL13-expressing ICAM-1\n                    <jats:sup>+<\/jats:sup>\n                    VCAM-1\n                    <jats:sup>+<\/jats:sup>\n                    follicular dendritic cells (FDCs) for the presence of antigen. CXCL13-CXCR5-mediated motility is mainly driven by the Rac guanine exchange factor DOCK2, which contains a binding domain for phosphoinositide-3,4,5-triphosphate (PIP3) and other phospholipids. While p110\u03b4, the catalytic subunit of the class IA phosphoinositide-3-kinase (PI3K) \u03b4, contributes to CXCR5-mediated B cell migration, the precise interdependency of DOCK2, p110\u03b4, or other PI3K family members during this process remains incompletely understood. Here, we combined\n                    <jats:italic>in vitro<\/jats:italic>\n                    chemotaxis assays and\n                    <jats:italic>in vivo<\/jats:italic>\n                    imaging to examine the contribution of these two factors during murine na\u00efve B cell migration to CXCL13. Our data confirm that p110\u03b4 is the main catalytic subunit mediating PI3K-dependent migration downstream CXCR5, whereas it does not contribute to chemotaxis triggered by CXCR4 or CCR7, two other chemokine receptors expressed on na\u00efve B cells. The contribution of p110\u03b4 activity to CXCR5-driven migration was complementary to that of DOCK2, and pharmacological or genetic interference with both pathways completely abrogated B cell chemotaxis to CXCL13. Intravital microscopy of control and gene-deficient B cells migrating on FDCs confirmed that lack of DOCK2 caused a profound migration defect, whereas p110\u03b4 contributed to cell speed and directionality. B cells lacking active p110\u03b4 also displayed defective adhesion to ICAM-1; yet, their migration impairment was maintained on ICAM-1-deficient FDCs. In sum, our data uncover two complementary signaling pathways mediated by DOCK2 and p110\u03b4, which enable CXCR5-driven na\u00efve B cell examination of FDCs.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.982383","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T13:34:26Z","timestamp":1666186466000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["DOCK2 and phosphoinositide-3 kinase \u03b4 mediate two complementary signaling pathways for CXCR5-dependent B cell migration"],"prefix":"10.3389","volume":"13","author":[{"given":"Stefanie","family":"Wissmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Stolp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Marcos","family":"J\u00edmenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens V.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81798-5","article-title":"A putative chemokine receptor, BLR1, directs b cell migration to defined lymphoid organs and specific anatomic compartments of the spleen","volume":"87","author":"F\u00f6rster","year":"1996","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/35018581","article-title":"A chemokine-driven positive feedback loop organizes lymphoid follicles","volume":"406","author":"Ansel","year":"2000","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-364273","article-title":"Lymph node b lymphocyte trafficking is constrained by anatomy and highly dependent upon chemoattractant desensitization","volume":"119","author":"Park","year":"2012","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-465336","article-title":"Naive b-cell trafficking is shaped by local chemokine availability and LFA-1\u2013independent stromal interactions","volume":"121","author":"Coelho","year":"2013","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/35090591","article-title":"Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration","volume":"412","author":"Fukui","year":"2001","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1084\/jem.20061780","article-title":"A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate\u2013mediated egress","volume":"204","author":"Nombela-Arrieta","year":"2007","journal-title":"J Exp Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2014.06.003","article-title":"Dock-family exchange factors in cell migration and disease","volume":"93","author":"Gadea","year":"2014","journal-title":"Eur J Cell Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/intimm\/dxz067","article-title":"DOCK family proteins: key players in immune surveillance mechanisms","volume":"32","author":"Kunimura","year":"2020","journal-title":"Int Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.1mr0520-221rr","article-title":"The regulation of DOCK family proteins on T and b cells","volume":"109","author":"Chen","year":"2021","journal-title":"J Leukoc. 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