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

Saved in:
Bibliographic Details
Published in:Pathogens (Basel) 2012-10, Vol.1 (2), p.83-101
Main Authors: Vrzalikova, Katerina, Leonard, Sarah, Fan, Yichao, Bell, Andrew, Vockerodt, Martina, Flodr, Patrik, Wright, Kenneth L, Rowe, Martin, Tao, Qian, Murray, Paul G
Format: Article
Language:English
Subjects:
Amino acids
BLIMP1
Cancer
Cell differentiation
Electronic mail systems
Epstein-Barr virus
Genes
Herpes viruses
Hodgkin’s lymphoma
hypomethylation
Inactivation
Infections
Leukemia
Lymphocytes
Lymphoma
Multiple myeloma
Pathogenesis
Pathogens
Proteins
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2076-0817
2076-0817
DOI:10.3390/pathogens1020083