{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:02:59Z","timestamp":1790251379826,"version":"4.1.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"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":[[2008,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rap1 is a small GTPase that belongs to Ras superfamily. This ubiquitously expressed GTPase is a key regulator of integrin functions. Rap1 exists in two isoforms: Rap1a and Rap1b. Although Rap1 has been extensively studied, its isoform-specific functions in B cells have not been elucidated. In this study, using gene knockout mice, we show that Rap1b is the dominant isoform in B cells. Lack of Rap1b significantly reduced the absolute number of B220+IgM\u2212 pro\/pre-B cells and B220+IgM+ immature B cells in bone marrow. In vitro culture of bone marrow-derived Rap1b\u2212\/\u2212 pro\/pre-B cells with IL-7 showed similar proliferation levels but reduced adhesion to stromal cell line compared with wild type. Rap1b\u2212\/\u2212 mice displayed reduced splenic marginal zone (MZ) B cells, and increased newly forming B cells, whereas the number of follicular B cells was normal. Functionally, Rap1b\u2212\/\u2212 mice showed reduced T-dependent but normal T-independent humoral responses. B cells from Rap1b\u2212\/\u2212 mice showed reduced migration to SDF-1, CXCL13 and in vivo homing to lymph nodes. MZ B cells showed reduced sphingosine-1-phosphate-induced migration and adhesion to ICAM-1. However, absence of Rap1b did not affect splenic B cell proliferation, BCR-mediated activation of Erk1\/2, p38 MAPKs, and AKT. Thus, Rap1b is crucial for early B cell development, MZ B cell homeostasis and T-dependent humoral immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.181.5.3373","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:32:15Z","timestamp":1397849535000},"page":"3373-3383","source":"Crossref","is-referenced-by-count":57,"title":["Rap1b Regulates B Cell Development, Homing, and T Cell-Dependent Humoral Immunity"],"prefix":"10.1093","volume":"181","author":[{"given":"Haiyan","family":"Chu","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aradhana","family":"Awasthi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Gilbert C","family":"White","sequence":"additional","affiliation":[{"name":"Laboratory of Platelet"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Chrzanowska-Wodnicka","sequence":"additional","affiliation":[{"name":"Vascular Signaling, Blood Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramaniam","family":"Malarkannan","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology"},{"name":"Division of Neoplastic Diseases and Related Disorders, Department of Medicine, and Department of Microbiology and Molecular Genetics, Medical College of Wisconsin , Milwaukee, WI 53226"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,9,1]]},"reference":[{"key":"2026012806253672600_R1","first-page":"77","article-title":"A Ras-related gene with transformation suppressor activity","volume-title":"Cell","year":"1989"},{"key":"2026012806253672600_R2","first-page":"2","article-title":"Chromosome mapping of the human Ras-related RAP1A, RAP1B, and RAP2 genes to chromosomes 1p12\u2014-p13, 12q14, and 13q34, respectively","volume-title":"Cytogenet. 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