Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation

Immunity. 2008 Jan;28(1):88-99. doi: 10.1016/j.immuni.2007.12.003.

Abstract

The integrin leukocyte function-associated antigen-1 (LFA-1) is important in the promotion of B cell adhesion, thereby facilitating immunological synapse (IS) formation and B cell activation. Despite this significance, the associated signaling mechanisms regulating LFA-1 activation remain elusive. Here, we show that both isoforms of the small GTPase Rac expressed by primary B cells, Rac1 and Rac2, were activated rapidly downstream of Src-family kinases, guanine-nucleotide exchange factors Vav1 and Vav2, and phosphoinositide-3 kinase (PI3K) after BCR engagement. We identify Rac2, but not Rac1, as critical for B cell adhesion to intercellular adhesion molecule-1 (ICAM-1) and IS formation. Furthermore, B cells expressing constitutively active Rac2 are highly adhesive. We observe that Rac2-deficient B cells exhibit lower amounts of Rap1-GTP and severe actin polymerization defects, identifying a potential mechanism underlying their behavior. We postulate that this critical role for Rac2 in mediating B cell adhesion and IS formation might apply in all lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / immunology*
  • Enzyme Activation / physiology*
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neuropeptides / immunology
  • Neuropeptides / metabolism
  • Proto-Oncogene Proteins c-vav / immunology
  • Proto-Oncogene Proteins c-vav / metabolism
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism*
  • Signal Transduction / immunology
  • Transfection
  • rac GTP-Binding Proteins / immunology
  • rac GTP-Binding Proteins / metabolism*
  • rac1 GTP-Binding Protein
  • src-Family Kinases / immunology
  • src-Family Kinases / metabolism

Substances

  • Neuropeptides
  • Proto-Oncogene Proteins c-vav
  • Rac1 protein, mouse
  • Receptors, Antigen, B-Cell
  • Vav1 protein, mouse
  • Vav2 protein, mouse
  • Intercellular Adhesion Molecule-1
  • src-Family Kinases
  • rac2 GTP-binding protein
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein