The Role of EBV LMP1 and LMP2 in B-cell Lymphoma

O'Donnel, M.A., Stevenson, D., Drotar, M. and Wilson, J.B. (2004) The Role of EBV LMP1 and LMP2 in B-cell Lymphoma. In: Keystone Symposia: Mouse Models of Human Cancer, Keystone, CO, USA, 17-22 Feb 2004,

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Abstract

The latent membrane proteins (LMP1 and LMP2) of Epstein-Barr virus (EBV) both impinge upon multiple cellular signalling pathways. LMP1, a viral onco-protein, can mimic a constitutively activated CD40 receptor in culture, activating NF-kB and JNK. Using EµLMP1 transgenic mice we find that some CD40 activities can be restored by LMP1 in CD40 null mice, in particular immunoglobulin isotype switching. We have previously shown that LMP2A allows the survival of B-cell receptor (BCR) negative B-cells in vivo (Caldwell et. al., 1998 Immunity 9:405-411) and have proposed this may be mediated by mimicking BCR survival signals. In support of this hypothesis, we will present data indicating that LMP2A expressing transgenic memory B-cells survive in the absence of antigen, using adoptive transfer experiments to CD40 null recipients. Furthermore, affinity maturation in the EµLMP2A mice may be impaired, again suggestive of BCR mediated survival instead of deletion of low affinity B-cells. Thus the activities of these two viral genes can promote B-cell survival and maturation, required in the EBV life cycle with the inadvertent consequence of predisposing the B-cell to lymphomagenesis.

Item Type:Conference Proceedings
Status:Published
Refereed:No
Glasgow Author(s) Enlighten ID:Stevenson, Dr David and Wilson, Professor Joanna and Drotar, Mr Mark
Authors: O'Donnel, M.A., Stevenson, D., Drotar, M., and Wilson, J.B.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences

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