TY - JOUR
T1 - 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
AU - Vrzalikova, Katerina
AU - Leonard, Sarah
AU - Fan, Yichao
AU - Bell, Andrew
AU - Vockerodt, Martina
AU - Flodr, Patrik
AU - Wright, Kenneth L.
AU - Rowe, Martin
AU - Tao, Qian
AU - Murray, Paul G.
PY - 2012/8/8
Y1 - 2012/8/8
N2 - 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.
AB - 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.
KW - BLIMP1
KW - Epstein-barr virus
KW - Hodgkin's lymphoma
KW - Hypomethylation
UR - http://www.scopus.com/inward/record.url?scp=84907288248&partnerID=8YFLogxK
U2 - 10.3390/pathogens1020083
DO - 10.3390/pathogens1020083
M3 - Article
AN - SCOPUS:84907288248
VL - 1
SP - 83
EP - 101
JO - Pathogens
JF - Pathogens
IS - 2
ER -