4IgB7‐H3 is the major isoform expressed on immunocytes as well as malignant cells

Abstract

Human B7‐H3, a novel member of B7 family, has two isoforms (2IgB7‐H3 and 4IgB7‐H3). As costimulatory functions of both isoforms are not clarified, there has been much discussion on their expression patterns, T‐cell responses, etc. This study generated two specific mouse anti‐human 2IgB7‐H3 monoclonal antibodies (mAbs) (7D7 and 10F1), whose specificities are quite different from those of the available B7‐H3 mAb (21D4) by competition assay. The use of antibodies indicated that B7‐H3 was found to have different expression patterns on monocyte‐derived dendritic cells, that is the isoform 2IgB7‐H3 is tended to express on immature dendritic cells (iDCs), whereas 4IgB7‐H3 could be detected in the whole process of maturation of dendritic cells. The isoform 4IgB7‐H3 was shown in the immunohistochemistry assay to be more widely expressed than 2IgB7‐H3 in human benign and malignant hepatic tissues. Furthermore, flow cytometry and reverse transcription–polymerase chain reaction indicated that 4IgB7‐H3 rather than 2IgB7‐H3 was the major isoform on many human tumor cell lines. In addition, both 2IgB7‐H3‐ and 4IgB7‐H3‐transfected cells could promote T‐cell proliferation, which could be blocked by 7D7 mAb. These two novel antibodies may shed light on the function of the two B7‐H3 isoforms.