Differential effects of interferon-gamma and low molecular weight BCGF on growth of human B lymphocytes; interferon-gamma prolongs the increased c-MYC mRNA levels after activation.
We have characterized the growth-stimulating effect of Interferon-gamma (IFN-gamma) on various parameters of B cell growth, and compared the effects with those of low molecular weight B cell growth factor (lmw BCGF). We have found that IFN-gamma did not affect early changes induced by anti-mu, like initial calcium-flux and rise in mRNA-and protein levels of the proto-oncogene c-myc measured at 3 h. On the other hand, IFN-gamma enhanced the effect of anti-mu on parameters measured later in the G1 phase of the cell cycle, such as expression of the transferrin receptor and general transcriptional activity, measured as an increase in 7-aminoactinomycin D binding. In particular, whereas the c-myc levels in anti-mu-treated cells peaked at 3 h and then gradually declined, IFN-gamma together with anti-mu maintained the c-myc levels at 24 h at approximately the same levels as seen at 3 h. Overall, lmw BCGF had a more potent effect on the parameters affected by IFN-gamma, correlating with stronger enhancement of DNA synthesis. However, in contrast to IFN-gamma lmw BCGF did not affect anti-mu-induced c-myc mRNA levels. Thus this study has revealed differences between two B cell growth factors in effects on B cell cycle parameters.
Lømo
J
J
Institute for Cancer Research, Norwegian Radium Hospital, Olso, Norway.
Smeland
E B
EB
Stokke
T
T
Holte
H
H
Funderud
S
S
Blomhoff
H K
HK
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007075:Immunoglobulin M; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects*; D011990:Receptors, Transferrin / Q000096:biosynthesis
D000888:Antibodies, Anti-Idiotypic; D005456:Fluorescent Dyes; D007075:Immunoglobulin M; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D003609:Dactinomycin; D015847:Interleukin-4; C025942:7-aminoactinomycin D; D007371:Interferon-gamma; D002118:Calcium