Experimental Cell Research 172 (1987) 101-109 Regulation of c-myc Transcription and Protein Expression during Activation of Normal Human B Cells ERLEND B. SMELAND,* KLAUS BEISKE,* BO EK,* ROSEMARY WATT,? SUSAN PFEIFER-OHLSSON,*%$ HEIDI KIIL BLOMHOFF,* TORE GODAL,* and ROLF OHLSSON*l t$ I *Laboratory of Immunology, Department of Pathology and the Norwegian Cancer Society, The Norwegian Radium Hospital, Montebello, N-0310 Oslo 3, Norway; tMoiecular Oncology Group, Smith Kline and French Laboratories, Philadelphia, Pennsylvania 19101; and #Centre for Biotechnology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden The close link between an actively expressed c-myc gene locus and cellular proliferation has been established in a variety of cell types. By using normal human peripheral ,blood B cells as a model for in uiuo quiescence, we have assessed the expression pattern of the c- myc gene in terms of transcriptional activation and concurrent production of c-myc protein, following induction by antibodies directed against antigens on the cell membrane. Both the lF5 monoclonal antibody, which reacts with the pan B cell antigen CD20, and the anti-p could promote transcriptional activation of the c-myc gene roughly corresponding to the increased levels of cytoplasmic c-myc mRNAs. In addition, more than 80% of the B cells could be induced to express c-myc protein by either stimulus. Since treatment only with polyclonal anti-p renders the B cells competent to proliferate in the presence of BCGF, c-myc protein expression is not per se sufficient for cell cycle progression into S phase. 0 1987 Academic Press, Inc. The potential of the retroviral v-myc oncogenes to promote uncontrolled cell proliferation of transformed target cells strongly suggests a dominant interferehce of the v-myc protein on normal regulatory growth processes [l-3]. In line with this view, a variety of quiescent cell phenotypes have been shown to respond to growth factors by induction of c-myc protooncogene expression during the Go/G1 transition [4-81. A central issue addresses to what extent the induced pattern of c- myc gene expression coincides with the execution of a c-myc function(s) in different phases of the cell cycle. Experiments carried out by Armelin et al. [9], involving a hormone-dependent mouse mammary tumor virus (MMTV) promoter conjugated to the c-myc gene, have shown that the transfected 3T3 cells acquired competence to respond to “progression factors” after exposure to glucocorticoid hormones. Moreover, microinjection of recombinant c-myc protein into quies- cent 3T3 cells renders the cells responsive to platelet-poor plasma promoting entry into the S phase [lo]. These results strongly suggest that the activated c- myc gene is a dominant feature of the early GI phase of 3T3 cells and may be involved in the induction of a competent state that will enable the cells to ’ To whom reprint requests should be addressed. Copyright 0 1987 by Academic Press. Inc. All rights of reproduction in any form reserved 0014-4827187 $03.00