EBV Conference 2008 Guangzhou - Baylor College of Medicine

121 (RegID: 1105; 1106)
Stephanie Medele
Institution: Helmholtz Zentrum München - German Reseach Centre for Environmental Health
e-mail: stephanie.medele@helmholtz-muenchen.de
EBV’S LATENT MEMBRANE PROTEIN 2A MIMICS BCR FUNCTIONS
Stephanie Medele, Liudmila Matskova, Dagmar Pich, Christoph Mancao, Wolfgang Hammerschmidt.
Posterabstract:
Hodgkin lymphoma, Burkitt lymphoma and post-transplantation lymphoma are associated with
Epstein-Barr virus and originate from clonal germinal centre (GC) B cells. During the process of somatic
hypermutation, GC B cells can acquire deleterious or other detrimental mutations in their immunoglobulin
genes, which can result in a non-functional B-cell receptor (BCR) or even loss of surface immunoglobulin
expression. In vivo these B cells are eliminated by immediate apoptosis as a rule. B cells latently infected
with EBV express the viral latent membrane protein 2A (LMP2A), which gives BCR-negative B cells a
selective advantage (Mancao and Hammerschmidt, Blood 2007, 110:3715-21). LMP2A and BCR are
structural homologous because they both contain a characteristic ITAM domain. Therefore, LMP2A might
mimic BCR signaling and provide BCR-low or BCR-negative B cells with a surrogate BCR-like signal to
escape negative selection in GC reactions.
In contrast to the BCR, LMP2A signaling has not been analyzed systematically because the viral protein is
constitutively active and independent of a ligand. Here we compare signaling activities and regulation of
cellular genes induced by the BCR and/or LMP2A in EBV-infected B cells. Cells were infected with either
wild-type EBV or viral mutants, which lack LMP2A or encode an inducible chimeric LMP2A molecule.
We found that both BCR and LMP2A signal through Syk, BLNK, PLC-γ2, Akt, IKKß and Erk. In a
microarray-based gene expression analysis many cellular genes show a very similar regulation by either
BCR or LMP2A indicating that both receptors affect similar functions in B cells. Our results indicate that
LMP2A can replace the BCR and explain why EBV-infected B cells, which express LMP2A, do not
undergo apoptosis in the absence of a BCR-derived signal. Our findings imply an important role for
EBV’s LMP2A in the process of lymphomagenesis in EBV-positive B-cell lymphomas.
EBV Conference 2008 Guangzhou
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