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.