NFκB induces overexpression of bovine FcRn: A novel mechanism that further contributes to the enhanced immune response in genetically modified animals carrying extra copies of FcRn

Judit Cervenak, Márton Doleschall, Balázs Bender, Balázs Mayer, Zita Schneider, Zoltán Doleschall, Yaofeng Zhao, Zsuzsanna Bosze, Lennart Hammarström, Wolfgang Oster, Imre Kacskovics

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8 Citations (Scopus)

Abstract

Among the many functions of the neonatal Fc receptor (FcRn) for IgG, it binds to IgG-opsonized antigen complexes and propagates their traffic into lysosomes where antigen processing occurs. We previously reported that transgenic (Tg) mice and rabbits that carry multiple copies and overexpress FcRn have augmented humoral immune responses. Nuclear factor-kappa B (NFκB) is a critical molecule in the signaling cascade in the immune response. NFκB induces human FcRn expression and our previous in silico analysis suggested NFκB binding sites in the promoter region of the bovine (b) FcRn α-chain gene (FCGRT). Here, we report the identification of three NFκB transcription factor binding sites in the promoter region of this gene using luciferase reporter gene technology, electromobility shift assay and supershift analysis. Stimulation of primary bovine endothelial cells with the Toll-like receptor-4 ligand lipopolysaccharide (LPS), which mediates its effect via NFκB, resulted in rapid upregulation of the bFcRn expression and a control gene, bovine E-selectin. This rapid bFcRn gene induction was also observed in the spleen of bFcRn Tg mice treated with intraperitoneally injected LPS, analyzed by northern blot analysis. Finally, NFκB-mediated bFcRn upregulation was confirmed at the protein level in macrophages isolated from the bFcRn Tg mice using flow cytometry with a newly developed FcRn specific monoclonal antibody that does not cross-react with the mouse FcRn. We conclude that NFκB regulates bFcRn expression and thus optimizes its functions, e.g., in the professional antigen presenting cells, and contributes to the much augmented humoral immune response in the bFcRn Tg mice.

Original languageEnglish
Pages (from-to)860-871
Number of pages12
JournalmAbs
Volume5
Issue number6
DOIs
Publication statusPublished - Nov 1 2013

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Keywords

  • Antigen presentation
  • FcRn
  • Humoral
  • IgG
  • Immune response
  • NFκB
  • Transgenic mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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