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  • Original Paper
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Disruption of the B-cell specific transcriptional program in HHV-8 associated primary effusion lymphoma cell lines

Oncogene volume 22, pages 964–973 (2003)Cite this article

Abstract

Primary effusion lymphoma (PEL) is a lymphoproliferative disease of B-cell origin that is associated with HHV-8 infection. PEL cells harbor a non-B, non-T phenotype and lack significant surface immunoglobulin (Ig) expression, a characteristic that has not been fully explained. In the present study, we demonstrate that PEL cells constitutively express interferon regulatory factor (IRF)-4, a transcription factor that regulates the activity of the immunoglobulin light-chain enhancer elements λB and κE3′ through binding to a composite Ets-IRF site. IRF-4 activity requires its physical interaction with PU.1, an Ets family member involved in the activation of genes essential for B-cell development. However, in PEL-derived B-cell lines, PU.1 expression was completely abrogated; expression of the B cell specific transcription factor Oct-2, which is known to regulate PU.1 expression, was also abolished. Moreover, the B-cell-specific coactivator of octamer factors, BOB-1/OcaB, was expressed at very decreased levels in PEL cells. Ectopic expression of Oct-2 was able to fully restore PU.1 promoter activity in the PEL cell line BCBL-1, while PU.1 expression also reconstituted the activity of the λB Ets-IRF site. In addition, protein levels of BSAP/Pax-5 and IRF-8/ICSBP were undetectable in PEL cells. The pattern of transcription factor ablation observed in PEL was found to be comparable to that observed in classical Hodgkin's disease-derived cell lines, which also lack B-cell-specific surface markers. These observations indicate that disruption of the B-cell-specific transcriptional program is likely to contribute to the incomplete B-cell phenotype characteristic of PEL cells.

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Acknowledgements

We gratefully acknowledge gifts of Oct-1 and Oct-2 expression vectors as well as murine PU.1 promoter luciferase reporter constructs from Dr Daniel G Tenen (Harvard University); the B4-TKCAT reporter construct from Dr Harinder Singh (University of Chicago) as well as the PU.1 expression vector from Dr Matthew Fenton (Boston University). We extend our gratitude to Dr Antonino Carbone for his kind gift of the PEL cell line CRO-AP6 and to Dr Sigrun Smola for her kind gift of Burkitt's lymphoma and Hodgking's lymphoma cell lines used in this study. Many thanks to Maria Ricci and to the members of the Molecular Oncology Group, Lady Davis Institute, McGill University, for their helpful discussion and technical assistance. This work was supported by Grants MOP42562 from the Canadian Institutes of Health Research.

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Authors and Affiliations

  1. Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, 3755 Cote-Ste., Catherine Road, Montreal, H3T-1E2, Quebec, Canada

    Meztli Arguello, Marco Sgarbanti, Eduardo Hernandez, Yael Mamane, Sonia Sharma, Marc Servant, Rongtuan Lin & John Hiscott

  2. Department of Microbiology and Immunology, McGill University, Montreal, H3T- 1E2, Canada

    Meztli Arguello, Yael Mamane, Sonia Sharma & John Hiscott

  3. Department of Medicine, McGill University, Montreal, H3T-1E2, Canada

    Marc Servant, Rongtuan Lin & John Hiscott

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  1. Meztli Arguello
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Correspondence to John Hiscott.

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Arguello, M., Sgarbanti, M., Hernandez, E. et al. Disruption of the B-cell specific transcriptional program in HHV-8 associated primary effusion lymphoma cell lines. Oncogene 22, 964–973 (2003). https://doi.org/10.1038/sj.onc.1206270

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