EBV Conference 2008 Guangzhou - Baylor College of Medicine

69 (RegID: 1676; 1678; 1679)
Martina Vockerodt
Institution: CRUK Institute for Cancer Studies, University of Birmingham
e-mail: m.vockerodt@bham.ac.uk
THE EPSTEIN-BARR VIRUS ONCOPROTEIN, LATENT MEMBRANE PROTEIN-1
REPROGRAMS TONSILLAR B CELLS TOWARDS A HODGKIN’S REED STERNBERG LIKE
PHENOTYPE
Martina Vockerodt,1 Katerina Vrzalikova1,2, Susan L Morgan,1 Wenbin Wei,1 Dieter Kube,3 Lawrence S
Young, 1 Ciaran B Woodman,1 and Paul G Murray1
1 School of Cancer Sciences, University of Birmingham, UK, 2 Laboratory of Molecular Pathology &
Department of Pathology, Faculty of Medicine, Palacky University, Olomouc, Czech Republic, 3 Zentrum
Innere Medizin, Abteilung Hämatologie und Onkologie, Georg-August-Universität Göttingen, Germany
Posterabstract:
Although the transforming capacities of the Epstein-Barr virus latent membrane protein-1 (LMP1) are
well established, its precise role in the development of EBV-associated lymphoma is poorly defined. As a
first step to better understand how LMP1 contributes to the early stages of B cell transformation, we
developed a method for the efficient expression of LMP1, and for the analysis of LMP1-induced signaling
pathways, in different subtypes of normal human tonsillar B cells. When expressed in germinal centre (GC)
B cells, LMP1 induced one-quarter of the transcriptional changes characteristic of Hodgkin’s lymphomas.
These changes included the striking down-regulation of B cell differentiation markers and of components
of B cell receptor (BCR) signaling such as CD79A, CD79B, CD19, CD20 and BLNK, and the
up-regulation of several anti-apoptotic genes (BCL2, CFLAR) and immunomodulatory molecules (CCL17,
LTA). Furthermore, LMP1 modulated the expression of B cell specific transcriptional regulators, such as
ID2, IRF4, MYC, EBF, SOX4 and PAX5. Importantly, the down-regulation of BCR signaling molecules
was also observed in LMP1-expressing naïve B cells, indicating that LMP1 might drive the differentiation
of these B cells towards a post- GC phenotype. Our results suggest that as well as providing a direct
anti-apoptotic signal, LMP1 might also contribute to B cell transformation by bypassing critical
checkpoints in B cell development.
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