%0 Journal Article
%T 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
%A Katerina Vrzalikova
%A Sarah Leonard
%A Yichao Fan
%A Andrew Bell
%A Martina Vockerodt
%A Patrik Flodr
%A Kenneth L. Wright
%A Martin Rowe
%A Qian Tao
%A Paul G. Murray
%J Pathogens
%D 2012
%I MDPI AG
%R 10.3390/pathogens1020083
%X B-lymphocyte-induced maturation protein 1 (BLIMP1) exists as two major isoforms, ¦Á and ¦Â, which arise from alternate promoters. Inactivation of the full length BLIMP1¦Á isoform is thought to contribute to B cell lymphomagenesis by blocking post-germinal centre (GC) B cell differentiation. In contrast, the shorter ¦Â isoform is functionally impaired and over-expressed in several haematological malignancies, including diffuse large B cell lymphomas (DLBCL). We have studied the influence on BLIMP1¦Â 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 BLIMP1¦Â 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 BLIMP1¦Â-specific promoter. Furthermore, we confirmed previous reports that the BLIMP1¦Â promoter is hypomethylated in DLBCL cell lines and show for the first time that BLIMP1¦Â is hypomethylated in the Hodgkin/Reed-Sternberg (HRS) cells of HL. Our results provide evidence in support of a role for BLIMP1¦Â in the pathogenesis of EBV-associated B cell lymphomas.
%K BLIMP1
%K Epstein-Barr virus
%K hypomethylation
%K Hodgkin¡¯s lymphoma
%U http://www.mdpi.com/2076-0817/1/2/83