Lipopolysaccharide and dexamethasone induce mouse mammary tumor proviral gene expression and differentiation in B lymphocytes through distinct regulatory pathways.
Endogenous mouse mammary tumor virus (MMTV) proviral transcripts are up regulated during the normal course of B-lymphocyte differentiation. We report here that the regulatory mechanisms which lead to increased levels of MMTV transcripts in differentiating, lipopolysaccharide (LPS)-stimulated normal B cells and in the inducible B-cell lymphoma line CH12 are at least partially distinct from those controlling increases in immunoglobulin and J-chain gene expression. In studies designed to characterize the stimulatory pathways leading to MMTV expression in CH12 cells, we found that stimulation with either LPS or dexamethasone (Dex), a transcriptional activator of MMTV genes, induced not only MMTV expression but also differentiation to antibody secretion. Only Dex-induced and not LPS-induced MMTV expression and differentiation were inhibited by the glucocorticoid antagonist RU486, demonstrating that Dex and LPS stimulate B cells by distinct molecular pathways. Therefore, in B cells, MMTV expression can be regulated via either the conventional hormone receptor-dependent pathway or a hormone receptor-independent pathway. Furthermore, these results suggest that steroid stimulation of B cells can lead to alterations in the expression of other results suggest that steroid stimulation of B cells can lead to alterations in the expression of other steroid-responsive genes that can become involved in the process of B-cell differentiation.
King
L B
LB
Department of Microbiology and Immunology, Duke Medical Center, Durham, North Carolina 27710.
Corley
R B
RB
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002472:Cell Transformation, Viral; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D015967:Gene Expression Regulation, Viral; D005803:Genes, Immunoglobulin / Q000187:drug effects; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008324:Mammary Tumor Virus, Mouse / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D011533:Proviruses / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D007148:Immunoglobulin mu-Chains; D008070:Lipopolysaccharides; D015735:Mifepristone; D003907:Dexamethasone