title: IFI16 Expression Is Related to Selected Transcription Factors during B-Cell Differentiation.
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.
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Hematopathology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Hematopathology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Agostinelli
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Hematopathology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fuligni
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Hematopathology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Righi
authors.affiliation: Department of Human Pathology, University of Palermo, 90127 Palermo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Microbiology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Re
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Microbiology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Clò
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Microbiology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Miserocchi
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Microbiology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morini
authors.affiliation: Department of Clinical and Experimental Medicine, Medical School of Novara, 28100 Novara, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Gariglio
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Otolaryngology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Gian Gaetano
authors.initials: GG
authors.lastname: Ferri
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Otolaryngology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rinaldi-Ceroni
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Otolaryngology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Piccin
authors.affiliation: Department of Public Health and Microbiology, University of Turin, 10126 Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Andrea
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School Unit of Hematopathology, S. Orsola Malpighi Hospital, 40138 Bologna, Italy.
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.affiliation: Department of Public Health and Microbiology, University of Turin, 10126 Turin, Italy.
authors.forename: Santo
authors.initials: S
authors.lastname: Landolfo
authors.affiliation: Department of Pathology and Diagnostic, University of Verona, 35124 Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
mesh_terms: D000328:Adult; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; C076700:IFI16 protein, human