BLIMP-1 is a target of cellular stress and downstream of the unfolded protein response

Eur J Immunol. 2006 Jun;36(6):1572-82. doi: 10.1002/eji.200535646.


B lymphocyte-induced maturation protein-1 (BLIMP-1) acts during differentiation of B cells and monocytes, but was originally identified as a repressor of the IFN-beta promoter induced during viral infection. A central regulator of the intracellular response to viral infection is the interferon-inducible double-stranded RNA activated protein kinase (PKR). PKR belongs to a family of kinases that phosphorylate the eukaryotic translation initiation factor 2-alpha (eIF2alpha) and activate common downstream signaling pathways. PERK, the endoplasmic reticulum resident PKR-homologue, is activated during the unfolded protein response (UPR), a stress response involved in both macrophage activation and terminal B-cell differentiation. This suggested that BLIMP-1 might be a target of stress responses involving PERK. We demonstrate that BLIMP-1 is rapidly up-regulated during the UPR in human myeloid and B-cell lines. This response is conserved in murine B-cells and murine macrophages, in which mimics of physiological stress and classical activation stimuli also induce Blimp-1. During the UPR, BLIMP-1 mRNA is induced at the level of transcription. This response is dependent on an intact PERK signaling pathway, independent of new protein synthesis and blocked by an inhibitor of NF-kappaB. Our data provide evidence for a novel pathway linking cellular stress to BLIMP-1, a regulator of differentiation in macrophages and B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cycloheximide / pharmacology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Dithiothreitol / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Eukaryotic Initiation Factor-2 / immunology
  • HL-60 Cells
  • HeLa Cells
  • Humans
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Positive Regulatory Domain I-Binding Factor 1
  • Protein Folding
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Regulatory Factor X Transcription Factors
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Sesquiterpenes / pharmacology
  • Sesquiterpenes, Guaiane
  • Signal Transduction
  • Thapsigargin / pharmacology
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • eIF-2 Kinase / immunology


  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Eukaryotic Initiation Factor-2
  • Nuclear Proteins
  • Prdm1 protein, mouse
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Regulatory Factor X Transcription Factors
  • Repressor Proteins
  • Sesquiterpenes
  • Sesquiterpenes, Guaiane
  • Transcription Factors
  • PRDM1 protein, human
  • helenalin
  • Thapsigargin
  • Cycloheximide
  • Positive Regulatory Domain I-Binding Factor 1
  • PERK kinase
  • eIF-2 Kinase
  • Dithiothreitol