Molecular basis of elevated c-myb expression in the abnormal L3T4-, Lyt-2- T lymphocytes of autoimmune mice.
The presence of the lpr/lpr genotype on a number of murine genetic backgrounds results in a systemic lupus erythematosus-like disease and lymphadenopathy. The T lymphocytes of these mice exhibit a variety of abnormalities; most pertinent to the present report is an abnormally high level of c-myb proto-oncogene mRNA. Since the c-myb protein is presumably the effector molecule that affects cellular functions, it is important to determine whether increased levels of this c-myb protein are produced. With the use of immunoprecipitation with an anti-v-myb reagent, we found high levels of c-myb protein in the lymph nodes of lpr mice. Detailed analysis showed that the c-myb protein is primarily expressed by an abnormal T lymphocyte population that does not express the mature T cell markers, L3T4 and Lyt-2. Analysis by two-dimensional gel electrophoresis showed that the c-myb proteins from normal thymocytes and from these L3T4-, Lyt-2-T cells are indistinguishable. DNA analysis with Southern hybridizations showed the lack of amplification, insertions, deletions, and rearrangements, which is in accord with results from the protein studies. Most interestingly, the c-myb gene in lpr L3T4-, Lyt-2- T cells is hypomethylated compared with normal controls. This suggests that a regulatory mechanism, rather than the structural alteration of the gene, is responsible for elevated expression of c-myb in these L3T4-, Lyt-2- cells.
Evans
J L
JL
Department of Microbiology/Immunology, University of North Carolina at Chapel Hill 27514.
Boyle
W J
WJ
Ting
J P
JP
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000032:analysis; D005260:Female; D005786:Gene Expression Regulation; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes / Q000032:analysis; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008815:Mice, Inbred Strains / Q000276:immunology; D008817:Mice, Mutant Strains / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
D000954:Antigens, Surface; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D004247:DNA