Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells

During the process of lymphocyte homing to secondary lymphoid organs, such as lymph nodes and tonsils, lymphocytes interact with and cross a specializ ed microvasculature, known as high endothelial venules, There is a great de al of information available about the first steps in the homing cascade, bu t molecular understanding of lymphocyte transmigration through the intercel lular junctions of high endothelial venules is lacking. In analyzing expres sed sequence tags from a cDNA library prepared from human tonsillar high en dothelial cells, we have identified a cDNA encoding a novel member of the i mmunoglobulin superfamily, The protein, which we have termed VE-JAM ("vascu lar endothelial junction-associated molecule"), contains two extracellular immunoglobulin-like domains, a transmembrane domain, and a relatively short cytoplasmic tail. VE-JAM is prominently expressed on high endothelial venu les but is also present on the endothelia of other vessels. Strikingly, it is highly localized to the intercellular boundaries of high endothelial cel ls. VE-JAM is most homologous to a recently identified molecule known as Ju nctional Adhesion Molecule, which is concentrated at the intercellular boun daries of both epithelial and endothelial cells. Because the Junctional Adh esion Molecule has been strongly implicated in the processes of neutrophil and monocyte transendothelial migration, an analogous function of VE-JAM du ring lymphocyte homing is plausible.