Carrasco Yolanda R, Batista Facundo D
Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
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.
血管细胞黏附分子-1（VCAM-1）是晚期抗原-4（VLA-4）的主要配体之一，VLA-4是一种在成熟B细胞表面高度表达的整合素。在此我们发现，在携带抗原的膜上共表达VCAM-1可促进B细胞活化。首先，这是通过介导B细胞 tethering实现的，这反过来又增加了B细胞被激活的可能性。其次，VLA-4与B细胞受体（BCR）协同作用，为B细胞提供紧密黏附并增强信号传导。当BCR对抗原的亲和力较低时，VCAM-1在促进B细胞活化中的这种双重作用最为有效。此外，我们表明单独的VCAM-1胞外域就足以执行此功能。然而，它需要跨膜结构域正确分离成B细胞免疫突触（IS）特有的对接结构。这些结果表明，膜抗原识别过程中VLA-4/VCAM-1的相互作用增强了B细胞活化，并且该功能似乎与其在IS处的最终外周定位无关。
