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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4627-4636. Prepublished online as a Blood First Edition Paper on March 4, 2008; DOI 10.1182/blood-2007-12-128140. This Article Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-12-128140v1 111/9/4627    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Wang, D. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Wang, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 7, 2007 Accepted February 29, 2008 A critical role of Rap1b in B cell trafficking and marginal zone B cell development Yuhong Chen, Mei Yu, Andrew Podd, Renren Wen, Magdalena Chrzanowska-Wodnicka, Gilbert C White, and Demin Wang* Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, United States State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Japan Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, United States * Corresponding author; email: demin.wang{at}bcw.edu. B cell development is orchestrated by complex signaling networks. Rap1 is a member of the Ras superfamily of small GTP binding proteins and has two isoforms, Rap1a and Rap1b. Although Rap1 has been implicated to have an important role in a variety of cellular processes, there is no direct evidence demonstrating a role of Rap1 in B cell biology. In this study, we find that Rap1b is the dominant isoform of Rap1 in B cells. We discover that Rap1b deficiency in mice barely affected early development of B cells, but markedly reduced marginal zone (MZ) B cells in the spleen and mature B cells in peripheral and mucosal lymph nodes. Rap1b-deficient B cells displayed normal survival and proliferation in vivo and in vitro. However, Rap1b-deficient B cells have impaired adhesion and reduced chemotaxis in vitro, and lessened homing to lymph nodes in vivo. Further, we find that Rap1b deficiency has no marked effect on LPS-, BCR- or SDF-1-induced activation of MAPKs and AKT, but clearly impairs SDF-1-mediated activation of Pyk-2, a key regulator of SDF-1-mediated B cell migration. Thus, we have discovered a critical and distinct role of Rap1b in mature B cell trafficking and development of MZ B cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. A. Durand, K. Hartvigsen, L. Fogelstrand, S. Kim, S. Iritani, B. Vanhaesebroeck, J. L. Witztum, K. D. Puri, and M. R. Gold Phosphoinositide 3-Kinase p110{delta} Regulates Natural Antibody Production, Marginal Zone and B-1 B Cell Function, and Autoantibody Responses J. Immunol., November 1, 2009; 183(9): 5673 - 5684. [Abstract] [Full Text] [PDF] Y. Katayama, M. Sekai, M. Hattori, I. Miyoshi, Y. Hamazaki, and N. Minato Rap signaling is crucial for the competence of IL-7 response and the development of B-lineage cells Blood, August 27, 2009; 114(9): 1768 - 1775. [Abstract] [Full Text] [PDF] H. Chu, A. Awasthi, G. C. White II, M. Chrzanowska-Wodnicka, and S. Malarkannan Rap1b Regulates B Cell Development, Homing, and T Cell-Dependent Humoral Immunity J. Immunol., September 1, 2008; 181(5): 3373 - 3383. [Abstract] [Full Text] [PDF]

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