Differential effects of transferrin receptor antibodies on growth and receptor 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 lymphocytes. These effects were also present using transferrin-free culture conditions. In this paper, we dissect cell membrane and intracellular events 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 surface in contrast to a downmodulation seen with other monoclonal antibodies 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 suggest that J64 causes a redistribution of transferrin receptor molecules from intracellular pools to the cell surface. Additional experiments investigating signal transduction mechanisms revealed no influence of J64 on intracellular Ca2+ concentrations or translocation of protein kinase C. However, an increase of transferrin receptor phosphorylation was seen in HL60 cells after treatment with phorbolester or J64. This phosphorylation of the transferrin receptor might be a signal transduction pathway involved in activation and growth control.