EBV Conference 2008 Guangzhou - Baylor College of Medicine

197 (RegID: 1723)
Katerina Vrzalikova
Institution: University of Birmingham
e-mail: kxv414@bham.ac.uk
THE OVERLAPPING TRANSCRIPTIONAL PROGRAMS OF LMP1 AND BLIMP1 SUPPORT A
CRITICAL ROLE FOR LMP1 IN THE ABERRANT DIFFERENTIATION OF B CELLS.
Katerina Vrzalikova1,2, Wenbin Wei1, Paul G Murray1, Ciaran B Woodman1 and Martina Vockerodt1
1School of Cancer Sciences, University of Birmingham, 2Laboratory of Molecular Pathology &
Department of Pathology, Faculty of Medicine, Palacky University, Olomouc, Czech Republic
Posterabstract:
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 which may contribute to the development of EBV
associated lymphomas, such as Hodgkin lymphoma. When expressed in GC B cells, LMP1 induces
transcriptional changes that show a striking overlap with those induced in the same cells by the B
lymphocyte-induced maturation protein-1 (BLIMP1), a key transcription factor that is essential for plasma
cell differentiation. For example, LMP1 and BLIMP1 coordinately regulate 230 genes, including the B
cell differentiation-associated transcription factors, BCL6, PAX5 and IRF4. However, this mimicry is only
partial, as unlike LMP1, BLIMP1 does not up-regulate the anti-apoptotic gene BCL2A1 or the chemokine
CCL22. In addition, a proposed function of LMP1 is the up-regulation of the inhibitor of DNA binding 2
(ID2), which can inhibit PAX5 mediated maintenance of B cell identity. However, ID2 is not regulated by
BLIMP1. Furthermore, the similarity between LMP1 and BLIMP1 targets is not a simple consequence of
BLIMP1 up-regulation by LMP1. Additionally, LMP1 down-regulates BLIMP1 in GC B cells. Our data
suggest that while LMP1-expressing cells are driven into the post-GC stages of B cell differentiation, they
fail to induce BLIMP1 and so are prevented from completing plasma cell differentiation. Given that
plasma cell differentiation is associated with induction of the virus replicative cycle, then the
LMP1-mediated disruption of this process could facilitate viral persistence.
EBV Conference 2008 Guangzhou
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