Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation.
Immunity, 2006/8;25(2):225-36.
Sciammas R[1], Shaffer AL, Schatz JH, Zhao H, Staudt LM, Singh H
Affiliations
PMID: 16919487
Impact factor: 43.474
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.
MeSH terms
Animals; B-Lymphocytes; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cytidine Deaminase; DNA; DNA-Binding Proteins; Gene Expression Profiling; Genome; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin Isotypes; Interferon Regulatory Factors; Mice; Mice, Knockout; Plasma Cells; Positive Regulatory Domain I-Binding Factor 1; Repressor Proteins; Transcription Factors
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