Volume 7 Supplement 1

Proceedings of the 13th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI)

Open Access

Epstein-Barr virus induces adhesion molecule CD226 (DNAM-1) expression during primary B cell transformation into lymphoblastoid cell lines

  • Lisa V Grossman1Email author,
  • Pavel A Nikitin1,
  • Sandeep Dave2,
  • Jason P Tourigny1 and
  • Micah A Luftig1
Infectious Agents and Cancer20127(Suppl 1):P31

https://doi.org/10.1186/1750-9378-7-S1-P31

Published: 19 April 2012

Epstein-Barr virus (EBV), an oncogenic herpesvirus associated with Burkitt’s lymphoma and other AIDS-related B cell malignancies, transforms primary human B cells into lymphoblastoid cell lines (LCLs) ex vivo. As LCLs express viral gene products similar to those found in EBV-mediated cancers, LCLs provide a practical model for tumorigenesis. Previous unpublished findings from our lab indicate that LCLs constitutively express the adhesion molecule CD226 (DNAM-1), found on virtually all peripheral blood NK cells, T cells, and monocytes, but only a small subset (~3%) of B cells. Although CD226 is known to mediate T-cell differentiation and cytotoxicity, NK cell cytotoxicity, NKT cell apoptosis, and monocyte extravasion, CD226 function in B cells remains relatively unstudied. Biochemically, CD226 functions to support the interaction between the intracellular adhesion molecules LFA-1 and ICAM-1. Here, we demonstrate that EBV specifically induces CD226 expression in primary human B cells and EBV-negative B lymphoblasts during viral-mediated proliferation and outgrowth. EBV infection of primary B cells increased CD226 surface expression 5-fold during early proliferation and approximately 30-fold upon transformation into LCLs. EBV-converted Burkitt’s lymphoma cells constitutively express CD226, while EBV-negative B cell lymphomas do not. Additionally, we demonstrate that LMP-1, an EBV latency III membrane oncoprotein, induces CD226 expression in EBV-negative Burkitt’s lymphoma cells. Finally, we demonstrate that the NFκB pathway regulates CD226 expression. Indeed, B cell lymphomas with high NFκB activity (activated B cell-like diffuse large B-cell lymphomas) express CD226 at higher levels than B cell lymphomas with low NFκB activity (germinal center B cell-like diffuse large B cell lymphomas). As CD226 supports the interaction between LFA-1 and ICAM-1, which is critical to maintain the constitutive aggregation of EBV-transformed B cells, we propose that EBV-mediated induction of CD226 drives cell-cell contact ensuring B cell survival. These data suggest that CD226, a newly identified EBV-induced cell adhesion molecule, may play a key role in the pathogenesis of AIDS-associated and other B cell lymphomas.

Authors’ Affiliations

(1)
Department of Molecular Genetics and Microbiology, Center for Virology, Duke University Medical Center
(2)
Duke Institute for Genome Sciences and Policy, Duke University

Copyright

© Grossman et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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