Bob1 (OCA-B/OBF-1) differential transactivation of the B cell-specific B29 (Ig beta) and mb-1 (Ig alpha) promoters.
The B29 (Igbeta) and mb-1 (Igalpha) gene products are B cell-specific essential components of the B cell receptor that are coexpressed at all stages of B cell differentiation, with the exception of plasma cells, which lack mb-1 expression. Transcription of both genes is governed by a similar cassette of interactive transcription factor-binding elements, including octamer motifs, in TATA-less promoters. In this study, we show the B cell-specific B29 gene promoter is transactivated in B and non-B cells by cotransfection with the B cell-specific octamer cofactor gene, Bob1 (OCA-B/OBF-1). The expression of Bob1 is also sufficient to override the silencing effects of the B29 silencer. This indicates that Bob1 plays a critical role in B cell-specific B29 promoter expression. In contrast, coexpression of Bob1 had no effect on mb-1 promoter activity. Bob1 transactivation only occurs with select octamer sequences that have an adenosine at position 5 (ATGCAAAT). The B29 promoter conforms to this consensus octamer motif, while the mb-1 promoter octamer motif does not. Octamer motif swapping between B29 and mb-1 promoters renders B29 unresponsive to Bob1 transactivation and makes mb-1 competent for Bob1 transactivation, thereby indicating that the B29 octamer motif is solely responsible for Bob1 interaction. Additionally, the mb-1 construct containing the B29 octamer motif is expressed in a plasmacytoma cell line, while the wild-type mb-1 promoter is not. Bob1 transactivation of B29 and the lack of this transactivation of mb-1 account for the differential expression of B29 and mb-1 in terminally differentiated plasma cells.
Malone
Cindy Sue
CS
Department of Microbiology and Immunology and Molecular Biology Institute, University of California School of Medicine, Los Angeles, CA 90095, USA.
Wall
Randolph
R
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051925:CD79 Antigens; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics; D018900:Dinucleotide Repeats / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D020868:Gene Silencing / Q000276:immunology; D051863:Host Cell Factor C1; D006801:Humans; D051379:Mice; D050811:Octamer Transcription Factor-1; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D004268:DNA-Binding Proteins; D018985:Epitopes, B-Lymphocyte; C497692:HCFC1 protein, human; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C091546:POU2AF1 protein, human; C494165:POU2F1 protein, human; C490424:Pou2af1 protein, mouse; C494166:Pou2f1 protein, mouse; D011947:Receptors, Antigen, B-Cell; D015534:Trans-Activators; D014157:Transcription Factors