Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas
B-lymphocyte-induced maturation protein 1 (BLIMP1) exists as two major isoforms, α and β, which arise from alternate promoters. Inactivation of the full length BLIMP1α isoform is thought to contribute to B cell lymphomagenesis by blocking post-germinal centre (GC) B cell differentiation. In contrast...
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MDPI AG
2012-10-01
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Online Access: | http://www.mdpi.com/2076-0817/1/2/83 |
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author | Katerina Vrzalikova Sarah Leonard Yichao Fan Andrew Bell Martina Vockerodt Patrik Flodr Kenneth L. Wright Martin Rowe Qian Tao Paul G. Murray |
author_facet | Katerina Vrzalikova Sarah Leonard Yichao Fan Andrew Bell Martina Vockerodt Patrik Flodr Kenneth L. Wright Martin Rowe Qian Tao Paul G. Murray |
author_sort | Katerina Vrzalikova |
collection | DOAJ |
description | B-lymphocyte-induced maturation protein 1 (BLIMP1) exists as two major isoforms, α and β, which arise from alternate promoters. Inactivation of the full length BLIMP1α isoform is thought to contribute to B cell lymphomagenesis by blocking post-germinal centre (GC) B cell differentiation. In contrast, the shorter β isoform is functionally impaired and over-expressed in several haematological malignancies, including diffuse large B cell lymphomas (DLBCL). We have studied the influence on BLIMP1β expression of the Epstein-Barr virus (EBV), a human herpesvirus that is implicated in the pathogenesis of several GC-derived lymphomas, including a subset of DLBCL and Hodgkin’s lymphoma (HL). We show that BLIMP1β expression is increased following the EBV infection of normal human tonsillar GC B cells. We also show that this change in expression is accompanied by hypomethylation of the BLIMP1β-specific promoter. Furthermore, we confirmed previous reports that the BLIMP1β promoter is hypomethylated in DLBCL cell lines and show for the first time that BLIMP1β is hypomethylated in the Hodgkin/Reed-Sternberg (HRS) cells of HL. Our results provide evidence in support of a role for BLIMP1β in the pathogenesis of EBV-associated B cell lymphomas. |
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issn | 2076-0817 |
language | English |
last_indexed | 2024-04-11T13:01:11Z |
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series | Pathogens |
spelling | doaj.art-05d3754645e247a9b069b3ebd3938abc2022-12-22T04:22:56ZengMDPI AGPathogens2076-08172012-10-01128310110.3390/pathogens1020083Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated LymphomasKaterina VrzalikovaSarah LeonardYichao FanAndrew BellMartina VockerodtPatrik FlodrKenneth L. WrightMartin RoweQian TaoPaul G. MurrayB-lymphocyte-induced maturation protein 1 (BLIMP1) exists as two major isoforms, α and β, which arise from alternate promoters. Inactivation of the full length BLIMP1α isoform is thought to contribute to B cell lymphomagenesis by blocking post-germinal centre (GC) B cell differentiation. In contrast, the shorter β isoform is functionally impaired and over-expressed in several haematological malignancies, including diffuse large B cell lymphomas (DLBCL). We have studied the influence on BLIMP1β expression of the Epstein-Barr virus (EBV), a human herpesvirus that is implicated in the pathogenesis of several GC-derived lymphomas, including a subset of DLBCL and Hodgkin’s lymphoma (HL). We show that BLIMP1β expression is increased following the EBV infection of normal human tonsillar GC B cells. We also show that this change in expression is accompanied by hypomethylation of the BLIMP1β-specific promoter. Furthermore, we confirmed previous reports that the BLIMP1β promoter is hypomethylated in DLBCL cell lines and show for the first time that BLIMP1β is hypomethylated in the Hodgkin/Reed-Sternberg (HRS) cells of HL. Our results provide evidence in support of a role for BLIMP1β in the pathogenesis of EBV-associated B cell lymphomas.http://www.mdpi.com/2076-0817/1/2/83BLIMP1Epstein-Barr virushypomethylationHodgkin’s lymphoma |
spellingShingle | Katerina Vrzalikova Sarah Leonard Yichao Fan Andrew Bell Martina Vockerodt Patrik Flodr Kenneth L. Wright Martin Rowe Qian Tao Paul G. Murray Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas Pathogens BLIMP1 Epstein-Barr virus hypomethylation Hodgkin’s lymphoma |
title | Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas |
title_full | Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas |
title_fullStr | Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas |
title_full_unstemmed | Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas |
title_short | Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas |
title_sort | hypomethylation and over expression of the beta isoform of blimp1 is induced by epstein barr virus infection of b cells potential implications for the pathogenesis of ebv associated lymphomas |
topic | BLIMP1 Epstein-Barr virus hypomethylation Hodgkin’s lymphoma |
url | http://www.mdpi.com/2076-0817/1/2/83 |
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