A role for interferon regulatory factor 4 in receptor editing

Simanta Pathak, Shibin Ma, Long Trinh, Runqing Lu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Receptor editing is the primary means through which B cells revise antigen receptors and maintain central tolerance. Previous studies have demonstrated that interferon regulatory factor 4 (IRF-4) and IRF-8 promote immunoglobulin light-chain rearrangement and transcription at the pre-B stage. Here, the roles of IRF-4 and -8 in receptor editing were analyzed. Our results show that secondary rearrangement was impaired in IRF-4 but not IRF-8 mutant mice, suggesting that receptor editing is defective in the absence of IRF-4. The role of IRF-4 in receptor editing was further examined in B-cell-receptor (BCR) transgenic mice. Our results show that secondary rearrangement triggered by membrane-bound antigen was defective in the IRF-4-deficient mice. Our results further reveal that the defect in secondary rearrangement is more severe at the immunoglobulin λ locus than at the κ locus, indicating that IRF-4 is more critical for the λ rearrangement. We provide evidence demonstrating that the expression of IRF-4 in immature B cells is rapidly induced by self-antigen and that the reconstitution of IRF-4 expression in the IRF-4 mutant immature B cells promotes secondary rearrangement. Thus, our studies identify IRF-4 as a nuclear effector of a BCR signaling pathway that promotes secondary rearrangement at the immature B-cell stage.

Original languageEnglish (US)
Pages (from-to)2815-2824
Number of pages10
JournalMolecular and cellular biology
Volume28
Issue number8
DOIs
StatePublished - Apr 1 2008

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B-Lymphoid Precursor Cells
interferon regulatory factor-4
Central Tolerance
B-Lymphocyte Subsets
Immunoglobulin Light Chains
B-Cell Antigen Receptors
Autoantigens
Transgenic Mice
Immunoglobulins
B-Lymphocytes
Antigens
Membranes
interferon regulatory factor-8

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

A role for interferon regulatory factor 4 in receptor editing. / Pathak, Simanta; Ma, Shibin; Trinh, Long; Lu, Runqing.

In: Molecular and cellular biology, Vol. 28, No. 8, 01.04.2008, p. 2815-2824.

Research output: Contribution to journalArticle

Pathak, Simanta ; Ma, Shibin ; Trinh, Long ; Lu, Runqing. / A role for interferon regulatory factor 4 in receptor editing. In: Molecular and cellular biology. 2008 ; Vol. 28, No. 8. pp. 2815-2824.
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