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Journal of Immunology Research
Volume 2015, Article ID 747645, 20 pages
http://dx.doi.org/10.1155/2015/747645
Research Article

IFI16 Expression Is Related to Selected Transcription Factors during B-Cell Differentiation

1Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Hematopathology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy
2Department of Human Pathology, University of Palermo, 90127 Palermo, Italy
3Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Microbiology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy
4Department of Clinical and Experimental Medicine, Medical School of Novara, 28100 Novara, Italy
5Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Otolaryngology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy
6Department of Public Health and Microbiology, University of Turin, 10126 Turin, Italy
7Department of Pathology and Diagnostic, University of Verona, 35124 Verona, Italy

Received 6 February 2015; Revised 27 April 2015; Accepted 14 May 2015

Academic Editor: Douglas C. Hooper

Copyright © 2015 Pier Paolo Piccaluga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The interferon-inducible DNA sensor IFI16 is involved in the modulation of cellular survival, proliferation, and differentiation. In the hematopoietic system, IFI16 is consistently expressed in the CD34+ stem cells and in peripheral blood lymphocytes; however, little is known regarding its regulation during maturation of B- and T-cells. We explored the role of IFI16 in normal B-cell subsets by analysing its expression and relationship with the major transcription factors involved in germinal center (GC) development and plasma-cell (PC) maturation. IFI16 mRNA was differentially expressed in B-cell subsets with significant decrease in IFI16 mRNA in GC and PCs with respect to naïve and memory subsets. IFI16 mRNA expression is inversely correlated with a few master regulators of B-cell differentiation such as BCL6, XBP1, POU2AF1, and BLIMP1. In contrast, IFI16 expression positively correlated with STAT3, REL, SPIB, RELA, RELB, IRF4, STAT5B, and STAT5A. ARACNE algorithm indicated a direct regulation of IFI16 by BCL6, STAT5B, and RELB, whereas the relationship between IFI16 and the other factors is modulated by intermediate factors. In addition, analysis of the CD40 signaling pathway showed that IFI16 gene expression directly correlated with NF-κB activation, indicating that IFI16 could be considered an upstream modulator of NF-κB in human B-cells.