TY - JOUR
T1 - The Epstein-Barr virus oncoprotein, latent membrane protein-1, reprograms germinal centre B cells towards a Hodgkin's Reed-Sternberg-like phenotype
AU - Vockerodt, Martina
AU - Morgan, SL
AU - Kuo, M
AU - Wei, Wenbin
AU - Chukwuma, MB
AU - Arrand, John
AU - Kube, D
AU - Gordon, J
AU - Young, Lawrence
AU - Woodman, Ciaran
AU - Murray, Paul
PY - 2008/9/1
Y1 - 2008/9/1
N2 - 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.
AB - 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.
KW - Epstein-Barr virus
KW - latent membrane protein-1
KW - Hodgkin's lymphoma
KW - gene expression
KW - germinal centre R cells
U2 - 10.1002/path.2384
DO - 10.1002/path.2384
M3 - Article
C2 - 18566961
SN - 1096-9896
VL - 216
SP - 83
EP - 92
JO - Journal of Pathology
JF - Journal of Pathology
IS - 1
ER -