B-cell activation by membrane-bound antigens is facilitated by the interaction of VLA-4 with VCAM-1.
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.
Carrasco
Yolanda R
YR
Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
Batista
Facundo D
FD
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
D000941:Antigens; D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1