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The Epstein–Barr virus oncoprotein, latent membrane protein‐1, reprograms germinal centre B cells towards a Hodgkin's Reed–Sternberg‐like phenotype
Author(s) -
Vockerodt M,
Morgan SL,
Kuo M,
Wei W,
Chukwuma MB,
Arrand JR,
Kube D,
Gordon J,
Young LS,
Woodman CB,
Murray PG
Publication year - 2008
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2384
Subject(s) - germinal center , phenotype , reed–sternberg cell , virology , virus , biology , epstein–barr virus , cancer research , antibody , immunology , genetics , gene , lymphoma , b cell , hodgkin lymphoma
Although the latent membrane protein‐1 (LMP1) of the Epstein–Barr virus (EBV) is believed to be important for the transformation of germinal centre (GC) B cells, the precise contribution of this viral oncogene to lymphoma development is poorly understood. In this study, we used a non‐viral vector‐based method to express LMP1 in primary human GC B cells. Gene expression profiling revealed that LMP1 induced in GC B cells transcriptional changes characteristic of Hodgkin's lymphoma cell lines. Strikingly, LMP1 down‐regulated the expression of B‐cell‐specific genes including B‐cell receptor components such as CD79A, CD79B, CD19, CD20, CD22, and BLNK. LMP1 also induced the expression of ID2, a negative regulator of B‐cell differentiation. Our data suggest that in EBV‐positive cases, LMP1 is likely to be a major contributor to the altered transcriptional pattern characteristic of Hodgkin/Reed–Sternberg cells, including the loss of B‐cell identity. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.