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 DAuthors
Magdalena Chrzanowska PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinDemin Wang PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Adjunct Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Gilbert C. White MD Professor in the Medicine department at Medical College of Wisconsin
MESH 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
