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c-MYC impairs immunogenicity of human B cells.

Adv. Cancer Res. 97, 167-188 (2007)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Deregulation of c-myc expression through chromosomal translocation is essential in the pathogenesis of Burkitt's lymphoma (BL). A characteristic feature of BL cells, compared to Epstein-Barr Virus (EBV)-immortalized B cells, is their lack of immunogenicity. To study the contribution of EBV genes and of the c-MYC protein to this phenotype, we have generated a conditional B cell system in which the viral proliferation program and expression of c-myc can be regulated independently of each other. In cells proliferating due to exogenous c-myc overexpression, the cell surface phenotype, the pattern of proliferation in single cell suspension, and the immunological characteristics of BL cells could be completely recapitulated. Yet, it had remained open whether nonimmunogenicity is the default phenotype when EBNA2 and LMP1 are switched off, or whether c-MYC actively contributes to immunosuppression. We provide evidence also for the latter by showing that c-MYC down-regulates genes of the NF-kappaB and interferon pathway in a dose-dependent fashion. c-MYC acts at at least two different levels, the level of interferon induction as well as at the level of action of type I and type II interferons on their respective target promoters. c-MYC does not block the interferon pathway completely, it shifts the balance and increases the threshold of interferon induction and action.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Epstein-barr-virus; Transcription factor IRF-1; African burkitt-lymphoma; Moloney leukemia-cells; Natural killer cells; I HLA expression; Nuclear antigen; Cancer immunosurveillance; Nasopharyngeal carcinoma; Immunoglobulin-synthesis
ISSN (print) / ISBN 0065-230x
Quellenangaben Band: 97, Heft: , Seiten: 167-188 Artikelnummer: , Supplement: ,
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed