B-cell activation by membrane-bound antigens is facilitated by the interaction of VLA-4 with VCAM-1

EMBO J. 2006 Feb 22;25(4):889-99. doi: 10.1038/sj.emboj.7600944. Epub 2006 Feb 2.


VCAM-1 is one of the main ligands of VLA-4, an integrin that is highly expressed on the surface of mature B cells. Here we find that coexpression of VCAM-1 on an antigen-bearing membrane facilitates B-cell activation. Firstly, this is achieved by mediating B-cell tethering, which in turn increases the likelihood of a B cell to be activated. Secondly, VLA-4 synergizes with the B-cell receptor (BCR), providing B cells with tight adhesion and enhanced signalling. This dual role of VCAM-1 in promoting B-cell activation is predominantly effective when the affinity of the BCR for the antigen is low. In addition, we show that the VCAM-1 ectodomain alone is sufficient to carry out this function. However, it requires the transmembrane domain to segregate properly into a docking structure characteristic of the B-cell immunological synapse (IS). These results show that the VLA-4/VCAM-1 interaction during membrane antigen recognition enhances B-cell activation and this function appears to be independent of its final peripheral localization at the IS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • B-Lymphocytes / immunology*
  • Cell Adhesion / immunology
  • Cell Membrane / immunology
  • Integrin alpha4beta1 / immunology*
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • NIH 3T3 Cells
  • Protein Binding / immunology
  • Protein Structure, Tertiary
  • Signal Transduction / immunology*
  • Vascular Cell Adhesion Molecule-1 / immunology*


  • Antigens
  • Integrin alpha4beta1
  • Vascular Cell Adhesion Molecule-1