The Epstein-Barr virus oncoprotein, latent membrane protein-1, reprograms germinal centre B cells towards a Hodgkin's Reed-Sternberg-like phenotype.
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.
Vockerodt
M
M
Cancer Research UK Institute for Cancer Studies, The Medical School, University of Birmingham, UK. m.vockerodt@bham.ac.uk
Morgan
S L
SL
Kuo
M
M
Wei
W
W
Chukwuma
M B
MB
Arrand
J R
JR
Kube
D
D
Gordon
J
J
Young
L S
LS
Woodman
C B
CB
Murray
P G
PG
D001402:B-Lymphocytes / Q000378:metabolism* / Q000821:virology; D006689:Hodgkin Disease / Q000235:genetics* / Q000821:virology; D006801:Humans; D010641:Phenotype; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000821:virology; D046888:Tissue Array Analysis / Q000379:methods; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins