The expression and regulation of c-myb transcription in B6/lpr Lyt-2-, L3T4-T lymphocytes.
Mice homozygous for the lpr gene spontaneously develop massive lymphoproliferation and an associated lupus-like autoimmune disease. In addition, the total lymphoid organs from these mice express high levels of mRNA for the c-myb proto-oncogene. Since enhanced c-myb mRNA is normally observed in immature thymic lymphocytes but not normal peripheral T cells, this may be indicative of the abnormal maturation state of lpr T lymphocytes. To determine whether the abnormal Lyt-2-, L3T4- (double negative) T lymphocytes in lpr mice express high c-myb, we purified this population by complement-mediated lysis with anti-L3T4 and Lyt-2 antibody from B6/lpr lymph nodes. We found that increased c-myb mRNA is expressed by this double-negative subset. To assess whether the high level of c-myb correlated with the aberrant undifferentiated state of these cells, we examined the effects of T cell differentiation inducers, phorbol ester and calcium ionophore, on c-myb expression. We found that c-myb levels were depressed after phorbol ester and calcium ionophore treatment. Concomitantly, transcriptional activation of the interleukin 2 receptor gene and progression of these cells through the cell cycle were observed. Thus, in B6/lpr double-negative T cells, the regulation of c-myb, interleukin 2 receptor, and cell proliferation may be interrelated. A combination of Northern hybridization and nuclear run-on transcription assays revealed two levels at which c-myb can be regulated in the double-negative T cell subset. The gene is transcriptionally regulated in untreated cells, but on induction with phorbol ester and calcium ionophore, the gene is negatively regulated via post-transcriptional mechanisms.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D000001:Calcimycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007376:Interleukin-2 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008198:Lymph Nodes / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate