{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:26:19Z","timestamp":1779888379197,"version":"3.53.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The Rho GTPase Cdc42 coordinates regulation of the actin and the microtubule cytoskeleton by binding and activating the Wiskott\u2013Aldrich syndrome protein. We sought to define the role of intrinsic expression of Cdc42 by mature B cells in their activation and function. Mice with inducible deletion of Cdc42 in mature B cells formed smaller germinal centers and had a reduced Ab response, mostly of low affinity to T cell\u2013dependent Ag, compared with wild-type (WT) controls. Spreading formation of long protrusions that contain F-actin, microtubules, and Cdc42-interacting protein 4, and assumption of a dendritic cell morphology in response to anti-CD40 plus IL-4 were impaired in Cdc42-deficient B cells compared with WT B cells. Cdc42-deficient B cells had an intact migratory response to chemokine in vitro, but their homing to the B cell follicles in the spleen in vivo was significantly impaired. Cdc42-deficient B cells induced a skewed cytokine response in CD4+ T cells, compared with WT B cells. Our results demonstrate a critical role for Cdc42 in the motility of mature B cells, their cognate interaction with T cells, and their differentiation into Ab-producing cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1401634","type":"journal-article","created":{"date-parts":[[2015,4,14]],"date-time":"2015-04-14T02:06:14Z","timestamp":1428977174000},"page":"4750-4758","source":"Crossref","is-referenced-by-count":26,"title":["The Rho GTPase Cdc42 Is Essential for the Activation and Function of Mature B Cells"],"prefix":"10.1093","volume":"194","author":[{"given":"Natalija","family":"Gerasimcik","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University , SE-106 91 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carin I M","family":"Dahlberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa A P","family":"Baptista","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel J","family":"Massaad","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital , Boston, MA 02115"},{"name":"Department of Pediatrics, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raif S","family":"Geha","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital , Boston, MA 02115"},{"name":"Department of Pediatrics, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa S","family":"Westerberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , SE-171 77 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Severinson","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University , SE-106 91 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,5,15]]},"reference":[{"key":"2025030706220117300_r1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/nature11738","article-title":"Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress","volume":"493","author":"Arnon","year":"2013","journal-title":"Nature"},{"key":"2025030706220117300_r2","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.cell.2010.10.032","article-title":"Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter","volume":"143","author":"Victora","year":"2010","journal-title":"Cell"},{"key":"2025030706220117300_r3","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1084\/jem.173.6.1297","article-title":"Adhesion of human B cells to follicular dendritic cells involves both the lymphocyte function-associated antigen 1\/intercellular adhesion molecule 1 and very late antigen 4\/vascular cell adhesion molecule 1 pathways","volume":"173","author":"Koopman","year":"1991","journal-title":"J. Exp. Med."},{"key":"2025030706220117300_r4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.1071632","article-title":"Integrin-mediated long-term B cell retention in the splenic marginal zone","volume":"297","author":"Lu","year":"2002","journal-title":"Science"},{"key":"2025030706220117300_r5","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.immuni.2013.08.038","article-title":"Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection","volume":"39","author":"Bannard","year":"2013","journal-title":"Immunity"},{"key":"2025030706220117300_r6","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/ni.2047","article-title":"The sphingosine 1-phosphate receptor S1P\u2082 maintains the homeostasis of germinal center B cells and promotes niche confinement","volume":"12","author":"Green","year":"2011","journal-title":"Nat. Immunol."},{"key":"2025030706220117300_r7","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1182\/blood.V98.4.1086","article-title":"Cdc42, Rac1, and the Wiskott-Aldrich syndrome protein are involved in the cytoskeletal regulation of B lymphocytes","volume":"98","author":"Westerberg","year":"2001","journal-title":"Blood"},{"key":"2025030706220117300_r8","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1182\/blood-2004-03-1003","article-title":"Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response","volume":"105","author":"Westerberg","year":"2005","journal-title":"Blood"},{"key":"2025030706220117300_r9","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1182\/blood-2008-02-140814","article-title":"Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis","volume":"112","author":"Meyer-Bahlburg","year":"2008","journal-title":"Blood"},{"key":"2025030706220117300_r10","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1182\/blood-2008-02-140715","article-title":"WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function","volume":"112","author":"Westerberg","year":"2008","journal-title":"Blood"},{"key":"2025030706220117300_r11","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1182\/blood-2010-09-308197","article-title":"Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function","volume":"119","author":"Westerberg","year":"2012","journal-title":"Blood"},{"key":"2025030706220117300_r12","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1084\/jem.20110200","article-title":"WASp-deficient B cells play a critical, cell-intrinsic role in triggering autoimmunity","volume":"208","author":"Becker-Herman","year":"2011","journal-title":"J. Exp. Med."},{"key":"2025030706220117300_r13","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1182\/blood-2011-09-379412","article-title":"B cell-intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice","volume":"119","author":"Recher","year":"2012","journal-title":"Blood"},{"key":"2025030706220117300_r14","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0960-9822(02)00423-2","article-title":"Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott-Aldrich syndrome","volume":"6","author":"Aspenstr\u00f6m","year":"1996","journal-title":"Curr. Biol."},{"key":"2025030706220117300_r15","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0092-8674(00)80732-1","article-title":"The interaction between N-WASP and the Arp2\/3 complex links Cdc42-dependent signals to actin assembly","volume":"97","author":"Rohatgi","year":"1999","journal-title":"Cell"},{"key":"2025030706220117300_r16","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1042\/BST0330891","article-title":"Rho GTPases and the control of cell behaviour","volume":"33","author":"Hall","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"2025030706220117300_r17","first-page":"1","article-title":"Roles of F-BAR\/PCH proteins in the regulation of membrane dynamics and actin reorganization","volume":"272","author":"Aspenstr\u00f6m","year":"2009","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"2025030706220117300_r18","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0960-9822(06)00219-3","article-title":"A Cdc42 target protein with homology to the non-kinase domain of FER has a potential role in regulating the actin cytoskeleton","volume":"7","author":"Aspenstr\u00f6m","year":"1997","journal-title":"Curr. Biol."},{"key":"2025030706220117300_r19","doi-asserted-by":"crossref","first-page":"7854","DOI":"10.1074\/jbc.275.11.7854","article-title":"Cdc42-interacting protein 4 mediates binding of the Wiskott-Aldrich syndrome protein to microtubules","volume":"275","author":"Tian","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2025030706220117300_r20","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1182\/blood.V96.1.234","article-title":"Integrin-associated protein\/CD47 regulates motile activity in human B-cell lines through CDC42","volume":"96","author":"Yoshida","year":"2000","journal-title":"Blood"},{"key":"2025030706220117300_r21","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1182\/blood-2009-04-214676","article-title":"Rho GTPase Cdc42 is essential for B-lymphocyte development and activation","volume":"114","author":"Guo","year":"2009","journal-title":"Blood"},{"key":"2025030706220117300_r22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1084\/jem.20141143","article-title":"Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity","volume":"212","author":"Burbage","year":"2015","journal-title":"J. Exp. Med."},{"key":"2025030706220117300_r23","doi-asserted-by":"crossref","first-page":"4675","DOI":"10.1091\/mbc.e06-05-0466","article-title":"Gene targeting of Cdc42 and Cdc42GAP affirms the critical involvement of Cdc42 in filopodia induction, directed migration, and proliferation in primary mouse embryonic fibroblasts","volume":"17","author":"Yang","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"2025030706220117300_r24","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.immuni.2012.11.015","article-title":"The BAFF receptor transduces survival signals by co-opting the B cell receptor signaling pathway","volume":"38","author":"Schweighoffer","year":"2013","journal-title":"Immunity"},{"key":"2025030706220117300_r25","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.immuni.2008.04.014","article-title":"Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development","volume":"28","author":"Kwon","year":"2008","journal-title":"Immunity"},{"key":"2025030706220117300_r26","doi-asserted-by":"crossref","first-page":"16252","DOI":"10.1073\/pnas.1002747107","article-title":"Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking","volume":"107","author":"Koduru","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030706220117300_r27","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1073\/pnas.96.5.2244","article-title":"Efficient IgG-mediated suppression of primary antibody responses in Fcgamma receptor-deficient mice","volume":"96","author":"Karlsson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030706220117300_r28","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1046\/j.1365-3083.1999.00539.x","article-title":"Characterization of CD40-dependent immunoglobulin class switching","volume":"49","author":"Str\u00f6m","year":"1999","journal-title":"Scand. J. Immunol."},{"key":"2025030706220117300_r29","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1084\/jem.20091489","article-title":"A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival","volume":"207","author":"Henderson","year":"2010","journal-title":"J. Exp. Med."},{"key":"2025030706220117300_r30","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1084\/jem.20052097","article-title":"SAP regulates T cell-mediated help for humoral immunity by a mechanism distinct from cytokine regulation","volume":"203","author":"Cannons","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025030706220117300_r31","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/nature07345","article-title":"SAP-controlled T-B cell interactions underlie germinal centre formation","volume":"455","author":"Qi","year":"2008","journal-title":"Nature"},{"key":"2025030706220117300_r32","doi-asserted-by":"crossref","first-page":"5366","DOI":"10.4049\/jimmunol.160.11.5366","article-title":"Regulation of cell morphology in B lymphocytes by IL-4: evidence for induced cytoskeletal changes","volume":"160","author":"Davey","year":"1998","journal-title":"J. Immunol."},{"key":"2025030706220117300_r33","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1189\/jlb.0803403","article-title":"The spreading of B lymphocytes induced by CD44 cross-linking requires actin, tubulin, and vimentin rearrangements","volume":"75","author":"Sumoza-Toledo","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"2025030706220117300_r34","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.cell.2004.06.027","article-title":"Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex","volume":"118","author":"Ho","year":"2004","journal-title":"Cell"},{"key":"2025030706220117300_r35","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.immuni.2007.04.008","article-title":"Definition of germinal-center B cell migration in vivo reveals predominant intrazonal circulation patterns","volume":"26","author":"Hauser","year":"2007","journal-title":"Immunity"},{"key":"2025030706220117300_r36","doi-asserted-by":"crossref","first-page":"925","DOI":"10.15252\/embj.201489732","article-title":"CD19 and BAFF-R can signal to promote B-cell survival in the absence of Syk","volume":"34","author":"Hobeika","journal-title":"EMBO J."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/10\/4750\/62233422\/1401634.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/10\/4750\/62233422\/1401634.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T07:22:49Z","timestamp":1741332169000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/194\/10\/4750\/7960846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2015,5,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1401634","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,5]]},"published":{"date-parts":[[2015,5]]}}}