title: Identification of a secondary promoter within the human B cell receptor component gene hCD79b.
abstract: The human B cell-specific protein, CD79b (also known as Igβ and B29) constitutes an essential signal transduction component of the B cell receptor. Although its function is central to the triggering of B cell terminal differentiation in response to antigen stimulation, the transcriptional determinants that control CD79b gene expression remain poorly defined. In the present study, we explored these determinants using a series of hCD79b transgenic mouse models. Remarkably, we observed that the previously described hCD79b promoter along with its associated enhancer elements and first exon could be deleted without appreciable loss of hCD79b transcriptional activity or tissue specificity. In this deletion setting, a secondary promoter located within exon 2 maintained full levels and specificity of hCD79b transcription. Of note, this secondary promoter was also active, albeit at lower levels, in the wild-type hCD79b locus. The activity of the secondary promoter was dependent on the action(s) of a conserved sequence element mapping to a chromatin DNase I hypersensitive site located within intron 1. mRNA generated from this secondary promoter is predicted to encode an Igβ protein lacking a signal sequence and thus unable to serve normal B cell receptor function. Although the physiologic role of the hCD79b secondary promoter and its encoded protein remain unclear, the current data suggest that it has the capacity to play a role in normal as well as pathologic states in B cell proliferation and function.
authors: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: Eung Jae
authors: EJ
authors: Yoo
authors: Nancy E
authors: NE
authors: Cooke
authors: Stephen A
authors: SA
authors: Liebhaber
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D051925:CD79 Antigens / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D051925:CD79 Antigens; C497883:CD79B protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011947:Receptors, Antigen, B-Cell; D019382:Human Growth Hormone
keywords: B Cell; DNase I Hypersensitive Site; Gene Expression; Immunology; Secondary Promoter; Transcription Enhancers; Transcription Promoter; Transgenic Mice; hCD79b
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