title: Differential Emu enhancer activity and expression of BOB.1/OBF.1, Oct2, PU.1, and immunoglobulin in reactive B-cell populations, B-cell non-Hodgkin lymphomas, and Hodgkin lymphomas.
abstract: It has previously been demonstrated that in cultured and in situ tumour cells of classical Hodgkin lymphoma (cHL), the immunoglobulin (Ig) promoter is inactive and its transcription factors Oct2 and/or BOB.1/OBF.1 are down-regulated. In this study, the analysis of these transcription factors has been extended to a broad spectrum of B-cell malignancies and the findings have been related to the situation in normal B-cells of various differentiation stages and to the expression of Ig. Furthermore, an additional Ig transcription factor, PU.1, recently described to be absent from cHL, and a further regulatory element of the Ig gene, the intronic Emu enhancer, have been studied. BOB.1/OBF.1 and Oct2 were present in all B-cells expressing Ig, whereas PU.1 proved to be absent from late B-cell differentiation stages and from a subset of germinal centre B-cells. Interestingly, there were several normal (eg germinal centre centroblasts and monocytoid B-cells) and malignant B-cell populations (eg a proportion of diffuse large B-cell lymphomas, DLBCLs) that were Ig-negative, despite their BOB.1/OBF.1 and Oct2 expression. This study further shows that absence of PU.1 alone, as well as inactivation of the intronic Emu enhancer, is not sufficient to down-regulate Ig transcription. Taken together, the simultaneous absence of PU.1, Oct2, and/or BOB.1/OBF.1 is unique to Hodgkin and Reed-Sternberg (HRS) cells and cannot be detected in normal B-cell subsets or B-cell non-Hodgkin lymphomas (B-NHLs). This supports the concept that the down-regulation of Ig in cHL does not reflect a physiological situation, but a defect probably closely linked to the pathogenesis of cHL.
authors.affiliation: Institute of Pathology, Consultation and Reference Centre for Lymph Node Pathology and Haematopathology, Benjamin Franklin University Hospital, Free University Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Korinna
authors.initials: K
authors.lastname: Jöhrens-Leder
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Foss
authors.forename: Franziska
authors.initials: F
authors.lastname: Jundt
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis / Q000235:genetics; D007075:Immunoglobulin M / Q000032:analysis / Q000235:genetics; D007136:Immunoglobulins / Q000032:analysis / Q000235:genetics*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007438:Introns / Q000235:genetics; D008221:Lymphoid Tissue / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D050813:Octamer Transcription Factor-2 / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007136:Immunoglobulins; D050813:Octamer Transcription Factor-2; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C091546:POU2AF1 protein, human