A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development

• Published in: Blood 2008-05, Vol.111 (9), p.4627-4636
• Main Authors: Chen, Yuhong, Yu, Mei, Podd, Andrew, Wen, Renren, Chrzanowska-Wodnicka, Magdalena, White, Gilbert C., Wang, Demin
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Chemokine CXCL12 - metabolism; Chemotaxis, Leukocyte; Focal Adhesion Kinase 2 - metabolism; Immunobiology; Lymph Nodes - cytology; Mice; rap GTP-Binding Proteins - deficiency; rap GTP-Binding Proteins - physiology; rap1 GTP-Binding Proteins - deficiency; rap1 GTP-Binding Proteins - physiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-12-128140

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.