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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- κ B activation, indicating that IFI16 could be considered an upstream modulator of NF- κ B in human B-cells.

IFI16Expression Is Related to Selected Transcription Factors during B-Cell Differentiation