The specific induction of myc protooncogene expression in normal human B cells is not a sufficient event for acquisition of competence to proliferate.
Resting human B cells can be activated to proliferate in the presence of both polyclonal antibodies to immunoglobulin mu heavy chains and B-cell growth factor (BCGF). This process appears to be temporally controlled in that the initial activation of the B cells and their responsiveness to BCGF is carried out by polyclonal anti-mu-chain antibodies alone. We have used this system to investigate the role of the c-myc gene in the cell cycle of normal human peripheral blood B cells. Our results show that the polyclonal anti-mu-chain antibody-induced B-cell activation is accompanied by a specific induction of c-myc gene expression without promoting subsequent entry into the S phase unless BCGF is added. Monoclonal antibodies to either mu chain or the pan-B-cell antigen Bp35 also revealed a similar G0-to-G1 transition and activation of c-myc gene expression. However, unlike activation with polyclonal anti-mu-chain antibodies, cells stimulated with these monoclonal antibodies do not acquire responsiveness to BCGF. The results imply that additional inducible functions must be present to potentiate the myc-specific function in order for the B cells to acquire the capacity to proliferate in response to BCGF. These findings are discussed in relation to the origin of B-cell malignancies.
D000888:Antibodies, Anti-Idiotypic; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology; D009857:Oncogenes
D000888:Antibodies, Anti-Idiotypic; D006133:Growth Substances; D007148:Immunoglobulin mu-Chains; D008222:Lymphokines; D015847:Interleukin-4