Soluble CD276 (B7-H3) is released from monocytes, dendritic cells and activated T cells and is detectable in normal human serum.

SummaryExpression of membrane CD276 (mB7-H3) has been reported on den-dritic cells (DCs), monocytes, activated T cells, and various carcinomacells. However, reports concerning its in vivo function have been inconsis-tent. Moreover, whether there is a soluble form of this protein is notknown. In this study, using a sensitive dual monoclonal antibody sand-wich enzyme-linked immunosorbent assay (ELISA) to detect the solubleform of B7-H3 (sB7-H3), we demonstrated the release of sB7-H3 bymonocytes, DCs, activated T cells, and various mB7-H3 + but not mB7-H3 – carcinoma cells. Release from cells was blocked by addition of amatrix metalloproteinase inhibitor (MMPI), which concomitantly causedthe accumulation of B7-H3 on the cell surface. To determine the level ofcirculating sB7-H3, more than 200 serum samples were included in thestudy. The results indicated that sB7-H3 was present at high levels in allserum samples. Western blotting of sB7-H3 from cell culture supernatantsor sera of healthy donors indicated that the molecular size was approxi-mately 16 kDa. Soluble B7-H3 was able to bind to the B7-H3 receptor(B7-H3R) on activated T cells, which showed that sB7-H3 is a function-ally active form. These results indicate that release of sB7-H3 from thecell surface is mediated by a matrix metalloproteinase and probably regu-lates B7-H3R/B7-H3 interactions in vivo. Cleavage of sB7-H3 to an activesoluble form would alter both proximal and distal cellular responses.Keywords: B7-H3; soluble; circulating; expression