DIFFERENTIAL-EFFECTS OF TRANSFERRIN RECEPTOR ANTIBODIES ON GROWTH ANDRECEPTOR EXPRESSION OF HUMAN LYMPHOCYTIC AND MYELOCYTIC CELL-LINES

J64, a monoclonal antibody against the human transferrin receptor, has been shown to induce interleukin-2 production by HUT78 cells. It also causes growth inhibition of several cell lines and stimulated lymphoc ytes. These effects were also present using transferrin-free culture c onditions. In this paper, we dissect cell membrane and intracellular e vents after binding of J64 and other transferrin receptor antibodies. Incubation of HUT78 and several other cell lines with J64 resulted in an increased number of receptor molecules expressed on the cell surfac e in contrast to a downmodulation seen with other monoclonal antibodie s to the transferrin receptor. This upregulation after treatment with J64 was not due to an increased concentration of transferrin receptor mRNA in these cells or a higher protein synthesis rate. We therefore s uggest that J64 causes a redistribution of transferrin receptor molecu les from intracellular pools to the cell surface. Additional experimen ts investigating signal transduction mechanisms revealed no influence of J64 on intracellular Ca2+ concentrations or translocation of protei n kinase C. However, an increase of transferrin receptor phosphorylati on was seen in HL60 cells after treatment with phorbolester or J64. Th is phosphorylation of the transferrin receptor might be a signal trans duction pathway involved in activation and growth control.