title: The VpreB1 enhancer drives developmental stage-specific gene expression in vivo.
abstract: In adult mice, the VpreB genes are expressed in bone marrow progenitor (pro-) and precursor (pre-) B cells. As part of the pre-B cell receptor, the proteins are crucial for the proliferation of these cells and consequently normal B lymphocyte development. Using cell lines, we identified a lineage- and developmental-stage-specific VpreB1 enhancer. Here, we analyze its specificity in vivo by generating transgenic mice in which expression of a reporter gene (human CD122) is regulated by the VpreB1 enhancer in the context of its own promoter. All transgenic lines expressed the reporter gene in the bone marrow in a copy number-independent manner, whereas expression levels were integration site-dependent. While the enhancer is not tissue specific, within the B cell lineage the expression pattern of human CD122 mimicked that of endogenous VpreB1. Thus, low levels were detected in pro-B cells, high levels in pre-BI and slightly lower levels in pre-BII cells; no expression was detected in immature/mature B cells. Furthermore, when in vitro cultured transgenic pre-B cells differentiated into immature B cells there was concomitant down-regulation of human CD122 and endogenous VpreB1. Thus the VpreB1 enhancer is sufficient to ensure developmental stage-specific expression of a reporter gene in B lymphocytes in vivo.
authors.affiliation: Developmental Immunology, The Babraham Institute, Cambridge, GB.
authors.forename: Steve
authors.initials: S
authors.lastname: Licence
authors.forename: Christine
authors.initials: C
authors.lastname: Persson
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mundt
authors.forename: Inga-Lill
authors.initials: IL
authors.lastname: Mårtensson
mesh_terms: D024506:5' Flanking Region; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D005803:Genes, Immunoglobulin; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2