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

Blood. 2008 May 1;111(9):4627-36. doi: 10.1182/blood-2007-12-128140. Epub 2008 Mar 4.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / physiology*
  • Chemokine CXCL12 / metabolism
  • Chemotaxis, Leukocyte*
  • Focal Adhesion Kinase 2 / metabolism
  • Lymph Nodes / cytology
  • Mice
  • rap GTP-Binding Proteins / deficiency
  • rap GTP-Binding Proteins / physiology*
  • rap1 GTP-Binding Proteins / deficiency
  • rap1 GTP-Binding Proteins / physiology*

Substances

  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Focal Adhesion Kinase 2
  • Ptk2b protein, mouse
  • Rap1b protein, mouse
  • rap GTP-Binding Proteins
  • rap1 GTP-Binding Proteins