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...

Full description

Bibliographic Details
Main Authors: Katerina Vrzalikova, Sarah Leonard, Yichao Fan, Andrew Bell, Martina Vockerodt, Patrik Flodr, Kenneth L. Wright, Martin Rowe, Qian Tao, Paul G. Murray
Format: Article
Language:English
Published: MDPI AG 2012-10-01
Series:Pathogens
Subjects:
Online Access:http://www.mdpi.com/2076-0817/1/2/83
_version_ 1798006784045088768
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.
first_indexed 2024-04-11T13:01:11Z
format Article
id doaj.art-05d3754645e247a9b069b3ebd3938abc
institution Directory Open Access Journal
issn 2076-0817
language English
last_indexed 2024-04-11T13:01:11Z
publishDate 2012-10-01
publisher MDPI AG
record_format Article
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
work_keys_str_mv AT katerinavrzalikova hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas
AT sarahleonard hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas
AT yichaofan hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas
AT andrewbell hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas
AT martinavockerodt hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas
AT patrikflodr hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas
AT kennethlwright hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas
AT martinrowe hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas
AT qiantao hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas
AT paulgmurray hypomethylationandoverexpressionofthebetaisoformofblimp1isinducedbyepsteinbarrvirusinfectionofbcellspotentialimplicationsforthepathogenesisofebvassociatedlymphomas