IRF4 Activity Is Required in Established Plasma Cells to Regulate Gene Transcription and Mitochondrial Homeostasis

Cell Rep. 2019 Nov 26;29(9):2634-2645.e5. doi: 10.1016/j.celrep.2019.10.097.

Abstract

The transcription factor interferon regulatory factor 4 (IRF4) is critical for the development, maintenance, and function of plasma cells. The mechanism by which IRF4 exerts its action in mature plasma cells has been elusive due to the death of all such cells upon IRF4 loss. While we identify apoptosis as a critical pathway for the death of plasma cells caused by IRF4 loss, we also determine that IRF4 did not regulate the intrinsic apoptotic pathway directly. By using an inducible IRF4 deletion system in the presence of the overexpression of anti-apoptotic BCL2, we identify genes whose expression is coordinated by IRF4 and that in turn specify plasma cell identity and mitochondrial homeostasis.

Keywords: BLIMP1; antibody; cell survival; gene expression; humoral immunity; metabolism; myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Homeostasis
  • Humans
  • Interferon Regulatory Factors / genetics*
  • Interferon Regulatory Factors / metabolism*
  • Mice
  • Mitochondria / genetics*
  • Mitochondria / metabolism*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Plasma Cells / physiology*
  • Plasmacytoma / genetics
  • Plasmacytoma / metabolism
  • Plasmacytoma / pathology
  • Transcription, Genetic

Substances

  • Interferon Regulatory Factors
  • interferon regulatory factor-4