Graded Expression of Interferon Regulatory Factor-4 Coordinates Isotype Switching with Plasma Cell Differentiation

Roger Sciammas, A. L. Shaffer, Jonathan H. Schatz, Hong Zhao, Louis M. Staudt, Harinder Singh

Research output: Contribution to journalArticle

332 Scopus citations

Abstract

Molecular mechanisms underlying the coordination of isotype switching with plasma cell differentiation are poorly understood. We show that interferon regulatory factor-4 (IRF-4) regulates both processes by controlling the expression of the Aicda and Prdm1 genes, which encode AID and Blimp-1, respectively. Genome-wide analysis demonstrated that Irf4-/- B cells failed to induce the entire Blimp-1-dependent plasma cell program. Restoration of AID or Blimp-1 expression in Irf4-/- B cells promoted isotype switching or secretion, respectively. IRF-4 was expressed in a graded manner in differentiating B cells and targeted Prdm1. Higher concentration of IRF-4 induced Prdm1 and consequently the transition from a germinal center gene expression program to that of a plasma cell. We propose a gene-regulatory network in which graded expression of IRF-4 developmentally coordinates isotype switching with plasma cell differentiation.

Original languageEnglish (US)
Pages (from-to)225-236
Number of pages12
JournalImmunity
Volume25
Issue number2
DOIs
StatePublished - Aug 2006
Externally publishedYes

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Keywords

  • DNA
  • MOLIMMUNO
  • SIGNALING

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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