A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development. Blood 2008 May 01;111(9):4627-36
Date
03/06/2008Pubmed ID
18319399Pubmed Central ID
PMC2343596DOI
10.1182/blood-2007-12-128140Scopus ID
2-s2.0-47149093727 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
B-cell development is orchestrated by complex signaling networks. Rap1 is a member of the Ras superfamily of small GTP-binding proteins and has 2 isoforms, Rap1a and Rap1b. Although Rap1 has been suggested to have an important role in a variety of cellular processes, no direct evidence demonstrates a role for Rap1 in B-cell biology. In this study, we found that Rap1b was the dominant isoform of Rap1 in B cells. We discovered 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 had impaired adhesion and reduced chemotaxis in vitro, and lessened homing to lymph nodes in vivo. Furthermore, we found that Rap1b deficiency had no marked effect on LPS-, BCR-, or SDF-1-induced activation of mitogen-activated protein kinases and AKT but clearly impaired 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.
Author List
Chen Y, Yu M, Podd A, Wen R, Chrzanowska-Wodnicka M, White GC, Wang DAuthor
Gilbert C. White MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsB-Lymphocytes
Chemokine CXCL12
Chemotaxis, Leukocyte
Focal Adhesion Kinase 2
Lymph Nodes
Mice
rap GTP-Binding Proteins
rap1 GTP-Binding Proteins
