Document Detail

B-cell activation by membrane-bound antigens is facilitated by the interaction of VLA-4 with VCAM-1.
MedLine Citation:
PMID:  16456548     Owner:  NLM     Status:  MEDLINE    
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.
Yolanda R Carrasco; Facundo D Batista
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-02
Journal Detail:
Title:  The EMBO journal     Volume:  25     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-22     Completed Date:  2006-04-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  889-99     Citation Subset:  IM    
Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
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MeSH Terms
Antigens / immunology
B-Lymphocytes / immunology*
Cell Adhesion / immunology
Cell Membrane / immunology
Integrin alpha4beta1 / immunology*
Lymphocyte Activation / immunology*
Mice, Transgenic
NIH 3T3 Cells
Protein Binding / immunology
Protein Structure, Tertiary
Signal Transduction / immunology*
Vascular Cell Adhesion Molecule-1 / immunology*
Reg. No./Substance:
0/Antigens; 0/Integrin alpha4beta1; 0/Vascular Cell Adhesion Molecule-1

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