Rap1b regulates B cell development, homing, and T cell-dependent humoral immunity. J Immunol 2008 Sep 01;181(5):3373-83
Date
08/21/2008Pubmed ID
18714009Pubmed Central ID
PMC4571460DOI
10.4049/jimmunol.181.5.3373Scopus ID
2-s2.0-51549097602 (requires institutional sign-in at Scopus site) 51 CitationsAbstract
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(-) pro/pre-B cells and B220(+)IgM(+) immature B cells in bone marrow. In vitro culture of bone marrow-derived Rap1b(-/-) pro/pre-B cells with IL-7 showed similar proliferation levels but reduced adhesion to stromal cell line compared with wild type. Rap1b(-/-) 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(-/-) mice showed reduced T-dependent but normal T-independent humoral responses. B cells from Rap1b(-/-) 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.
Author List
Chu H, Awasthi A, White GC 2nd, Chrzanowska-Wodnicka M, Malarkannan SAuthors
Magdalena Chrzanowska PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of WisconsinSubramaniam Malarkannan PhD Professor in the Medicine 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
AnimalsAntibody Formation
B-Lymphocytes
Bone Marrow
Cell Adhesion
Cell Proliferation
Cells, Cultured
Chemotaxis, Leukocyte
Lymph Nodes
Mice
Mice, Knockout
Spleen
T-Lymphocytes
rap GTP-Binding Proteins