PMID- 2157765 OWN - NLM STAT- MEDLINE DCOM- 19900517 LR - 20141120 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 144 IP - 8 DP - 1990 Apr 15 TI - Molecular events in B lymphocyte differentiation. Inducible expression of the endogenous mouse mammary tumor proviral gene, Mtv-9. PG - 3218-27 AB - We have previously shown that the steady state levels of transcripts encoded by an endogenous mouse mammary tumor virus (MMTV) increase during LPS-induced differentiation of both normal B lymphocytes and an inducible B cell lymphoma, CH12. A large body of evidence suggests that MMTV expression is primarily limited to mammary tissues and that expression in cell lines from nonmammary tissues is accompanied by viral amplification and alterations in the transcriptional control regions of the viral long terminal repeat. We have, therefore, carefully characterized MMTV expression in CH12 cells and in other cells of the B lineage in order to determine if the expression of MMTV transcripts in differentiating B cells results from the "abnormal" transcriptional regulation seen in other nonmammary tissue. In this manuscript, we present evidence that MMTV transcripts are expressed in a variety of cells of the B lineage and that the levels of constitutive expression vary among the different cells. On the other hand, T cell lymphomas lacking amplified MMTV do not contain proviral transcripts, suggesting that MMTV transcription may be preferentially expressed in B lymphocytes. We demonstrate that MMTV transcripts are up-regulated during cytokine-mediated as well as LPS-mediated differentiation, and that most, if not all, expression is due to the activity of a single proviral gene, Mtv-9, in CH12 cells. Furthermore, the expression of MMTV transcripts in CH12 cells neither requires nor is accompanied by amplification of the provirus. Sequence analysis demonstrates that the U3 region of the expressed Mtv-9 long terminal repeat contains neither deletions nor insertions, and the well-characterized enhancer and promoter sites in the glucocorticoid response element which are known to be involved in transcriptional regulation of MMTV in mammary tissues have not been disrupted. These data suggest that the Mtv-9 locus behaves as a normal somatic gene which is differentially regulated during B cell development and differentiation. Unlike the events which lead to MMTV expression in other nonmammary tissues, B cells may express transcription factor(s) which are capable of inducing expression of endogenous MMTV proviral genes during the natural course of differentiation. Analysis of the mechanisms which control the expression of this gene should be useful in characterizing the molecular events which govern B cell differentiation. FAU - King, L B AU - King LB AD - Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710. FAU - Lund, F E AU - Lund FE FAU - White, D A AU - White DA FAU - Sharma, S AU - Sharma S FAU - Corley, R B AU - Corley RB LA - eng SI - GENBANK/M29600 GR - 5 T32 CA09058/CA/NCI NIH HHS/United States GR - 5 T32 GM07184/GM/NIGMS NIH HHS/United States GR - CA36642/CA/NCI NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Gene Products, env) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Viral) SB - IM MH - Animals MH - B-Lymphocytes/*cytology/microbiology/physiology MH - Base Sequence MH - Blotting, Southern MH - Cell Differentiation/drug effects MH - Cloning, Molecular MH - Gene Amplification MH - Gene Expression Regulation/drug effects MH - Gene Products, env/genetics MH - Genes, Viral MH - In Vitro Techniques MH - Lipopolysaccharides/pharmacology MH - Mammary Tumor Virus, Mouse/*genetics MH - Mice MH - Molecular Sequence Data MH - RNA, Viral/biosynthesis MH - Restriction Mapping MH - T-Lymphocytes/microbiology/physiology MH - Transcription, Genetic MH - Tumor Cells, Cultured EDAT- 1990/04/15 00:00 MHDA- 1990/04/15 00:01 CRDT- 1990/04/15 00:00 PHST- 1990/04/15 00:00 [pubmed] PHST- 1990/04/15 00:01 [medline] PHST- 1990/04/15 00:00 [entrez] PST - ppublish SO - J Immunol. 1990 Apr 15;144(8):3218-27.