Type I interferons directly down-regulate BCL-6 in primary and transformed germinal center B cells: Differential regulation in B cell lines derived from endemic or sporadic Burkitt's lymphoma

Daniel Salamon, Monika Adori, Minghui He, Peter Bönelt, Eva Severinson, Lorand L. Kis, Liang Wu, Dorina Ujvari, Benjamin Leveau, Noemi Nagy, George Klein, Eva Klein

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Type I interferons (IFN) exert multiple effects on both the innate and adaptive immune system in addition to their antiviral and antiproliferative activities. Little is known, however about the direct effects of type I IFNs on germinal center (GC) B cells, the central components of adaptive B cell responses. We used Burkitt's lymphoma (BL) lines, as a model system of normal human GC B cells, to examine the effect of type I IFNs on the expression of BCL-6, the major regulator of the GC reaction. We show that type I IFNs, but not IFNγ, IL-2 and TNFα rapidly down-regulate BCL-6 protein and mRNA expression, in cell lines derived from endemic, but not from sporadic BL. IFNα-induced down-regulation is specific for BCL-6, independent of Epstein-Barr virus and is not accompanied by IRF-4 up-regulation. IFNα-induced BCL-6 mRNA down-regulation does not require de novo protein synthesis and is specifically inhibited by piceatannol. The proteasome inhibitor MG132 non-specifically prevents, while inhibitors of alternate type I IFN signaling pathways do not inhibit IFNα-induced BCL-6 protein downregulation. We validate our results with showing that IFNα rapidly down-regulates BCL-6 mRNA in purified mouse normal GC B cells. Our results identify type I IFNs as the first group of cytokines that can down-regulate BCL-6 expression directly in GC B cells.

Original languageEnglish
Pages (from-to)360-371
Number of pages12
JournalCytokine
Volume57
Issue number3
DOIs
Publication statusPublished - Mar 1 2012

Keywords

  • BCL-6
  • Burkitt's lymphoma
  • Type I interferons

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Type I interferons directly down-regulate BCL-6 in primary and transformed germinal center B cells: Differential regulation in B cell lines derived from endemic or sporadic Burkitt's lymphoma'. Together they form a unique fingerprint.

  • Cite this