Transcriptional activation of the Pirb gene in B cells by PU.1 and Runx3

J Immunol. 2011 Jun 15;186(12):7050-9. doi: 10.4049/jimmunol.1001302. Epub 2011 May 9.


Cells in the immune system are regulated positively or negatively by sets of receptor pairs that conduct balanced, activating, or inhibitory intracellular signaling. One such receptor pair termed paired Ig-like receptor (PIR) is composed of the inhibitory PIR-B and its activating isoform, PIR-A. Upon binding to their shared ligand, MHC class I molecules, these receptors control the threshold for immune cell activation. Gene-targeting studies on PIR-B in mice revealed the importance of the inhibition mediated by the PIR-B-MHC interaction in the immune system. Recent studies also revealed the significance of the interaction of PIR-B with neurite outgrowth inhibitors, including Nogo in the CNS. The coordinated regulation by PIR-B and PIR-A is considered to be primarily dependent on their expression balance in cells. However, the mechanism underlying transcriptional control of the genes for PIR-B and PIR-A (Pirb and Pira, respectively) remains to be clarified. In this study, we identified the major cis-acting promoter segment for Pirb and Pira in B cells as the -212 to -117 region upstream from the translation initiation codon. PU.1 and Runx3 were found to bind to this Pirb promoter. Truncation of the PU.1-binding motif significantly reduced the promoter activity, whereas the influence of elimination of the Runx3 site was marginal in B lymphoma BCL1-B20 cells. Unexpectedly, PU.1, but not Runx3, knockdown reduced the levels of both the Pirb and Pira transcripts. We conclude that the major promoter of Pirb, and probably Pira as well, is activated dominantly by PU.1 and marginally by Runx3 in B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Binding Sites
  • Cell Line, Tumor
  • Core Binding Factor Alpha 3 Subunit / genetics*
  • Core Binding Factor Alpha 3 Subunit / physiology
  • Lymphoma, B-Cell / genetics
  • Mice
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology
  • Receptors, Immunologic / genetics*
  • Trans-Activators / genetics*
  • Trans-Activators / physiology
  • Transcriptional Activation / genetics*


  • Core Binding Factor Alpha 3 Subunit
  • Pirb protein, mouse
  • Proto-Oncogene Proteins
  • Receptors, Immunologic
  • Runx3 protein, mouse
  • Trans-Activators
  • proto-oncogene protein Spi-1

Associated data

  • RefSeq/NM_011095