CHARACTERIZATION OF A CELL-SURFACE GLYCOPROTEIN IPO-3, EXPRESSED ON ACTIVATED HUMAN B-LYMPHOCYTES AND T-LYMPHOCYTES

We characterize the expression, biochemical structure, and function of a novel glycoprotein, IPO-3, up-regulated on activated human lymphocy tes. IPO-3 is found on activated B cells, B cell lines, and hairy cell leukemias but is not expressed on T cell or nonlymphoid cell lines. I PO-3 is not B cell-specific as it is detected at low levels on CD45ROCD45RA- peripheral blood T cells and CD4+CD8+CD45RO+CD45RA- thymocytes . The IPO-3 Ag is a single-chain heavily N-glycosylated phosphoglycopr otein approximately 75 to 95 kDa in size with a 42-kDa protein core. I n vitro kinase assays revealed that IPO-3 has a protein kinase activit y associated with it that is maintained even in Nonidet P-40 lysates. IPO-3 is up-regulated on resting B cells within 16 h after activation with different signals including anti-IgM, IL-4, or mAb to CD40, CD20, or Bgp95. It could also be induced on T cells via CD3-cross-linking, but the kinetics of IPO-3 induction was slower on T cells than on B ce lls. Cross-linking IPO-3 on B cells with mAb did not induce proliferat ion alone but did augment proliferation promoted by IL-4 and anti-CD40 and did trigger increases in [Ca2+]i in resting B cells. Binding of I PO-3 could not be inhibited by a variety of mAb to previously identifi ed activation markers. Thus, the IPO-3 glycoprotein appears to be a no vel marker of activated B and T lymphocytes, which may play a role in the regulation of lymphocyte activation.