APRIL stimulates NF-κB-mediated HoxC4 induction for AID expression in mouse B cells

Seok Rae Park, Pyeung Hyeun Kim, Kyu Seon Lee, Sang Hoon Lee, Goo Young Seo, Yung Choon Yoo, Junglim Lee, Paolo Casali

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Activation-induced cytidine deaminase (AID) plays a key role in B cell immunoglobulin (Ig) class switch recombination (CSR) and somatic hypermutation (SHM). We have previously reported that the highly conserved homeodomain HoxC4 transcription factor binds to the Aicda (AID gene) promoter to induce AID expression. Here, we investigated the regulation of HoxC4 transcription by a proliferation-inducing ligand (APRIL) and B cell-activating factor belonging to the TNF family (BAFF) in mouse B cells. APRIL substantially increased both HoxC4 and AID expression, whereas BAFF induced the expression of AID but not HoxC4. To elucidate the underlying mechanisms, we constructed a HoxC4 gene promoter reporter vector and analyzed the promoter induction after APRIL stimulation. APRIL enhanced the HoxC4 promoter activity by 2.3-fold, and this increase disappeared when the second putative NF-κB-binding promoter element (NBE2) was mutated. Based on ChIP assays, we found that NF-κB bound to the HoxC4 promoter NBE2 region. Furthermore, the overexpression of NF-κB augmented the APRIL-induced HoxC4 promoter activity, while the expression of dominant negative-IκBα suppressed it. Taken together, our findings suggest that NF-κB mediates APRIL-induced HoxC4 transcription.

Original languageEnglish (US)
Pages (from-to)608-613
Number of pages6
JournalCytokine
Volume61
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • AID
  • APRIL
  • B cells
  • HoxC4
  • NF-κB

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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  • Cite this

    Park, S. R., Kim, P. H., Lee, K. S., Lee, S. H., Seo, G. Y., Yoo, Y. C., Lee, J., & Casali, P. (2013). APRIL stimulates NF-κB-mediated HoxC4 induction for AID expression in mouse B cells. Cytokine, 61(2), 608-613. https://doi.org/10.1016/j.cyto.2012.10.018