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BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway

Author

Listed:
  • Egest J. Pone

    (Institute for immunology and School of Medicine, University of California)

  • Jinsong Zhang

    (Institute for immunology and School of Medicine, University of California
    Present address: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.)

  • Thach Mai

    (Institute for immunology and School of Medicine, University of California)

  • Clayton A. White

    (Institute for immunology and School of Medicine, University of California)

  • Guideng Li

    (Institute for immunology and School of Medicine, University of California)

  • John K. Sakakura

    (Institute for immunology and School of Medicine, University of California)

  • Pina J. Patel

    (Institute for immunology and School of Medicine, University of California)

  • Ahmed Al-Qahtani

    (Institute for immunology and School of Medicine, University of California
    Present address: UAE University, Faculty of Medicine and Health Sciences, P.O. Box 17666, Al-Ain, United Arab Emirates.)

  • Hong Zan

    (Institute for immunology and School of Medicine, University of California)

  • Zhenming Xu

    (Institute for immunology and School of Medicine, University of California)

  • Paolo Casali

    (Institute for immunology and School of Medicine, University of California)

Abstract

By diversifying antibody biological effector functions, class switch DNA recombination has a central role in the maturation of the antibody response. Here we show that BCR-signalling synergizes with Toll-like receptor (TLR) signalling to induce class switch DNA recombination. BCR-signalling activates the non-canonical NF-κB pathway and enhances the TLR-dependent canonical NF-κB pathway, thereby inducing activation-induced cytidine deaminase (AID), which is critical for class switch DNA recombination. Escherichia coli lipopolysaccharide (LPS) triggers dual TLR4/BCR-signalling and induces hallmarks of BCR-signalling, including CD79a phosphorylation and Ca2+ mobilization, and activates both the NF-κB pathways to induce AID and class switch DNA recombination in a PI(3)K p85α-dependent fashion. CD40-signalling activates the two NF-κB pathways to induce AID and class switch DNA recombination independent of BCR-signalling. Finally, dual BCR/TLR-engaging NP–lipopolysaccharide effectively elicits class-switched NP-specific IgG3 and IgG2b in mice. Thus, by integrating signals of the non-canonical and canonical NF-κB pathways, BCR and TLRs synergize to induce AID and T-cell-independent class switch DNA recombination.

Suggested Citation

  • Egest J. Pone & Jinsong Zhang & Thach Mai & Clayton A. White & Guideng Li & John K. Sakakura & Pina J. Patel & Ahmed Al-Qahtani & Hong Zan & Zhenming Xu & Paolo Casali, 2012. "BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1769
    DOI: 10.1038/ncomms1769
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    Cited by:

    1. Yijiang Xu & Hang Zhou & Ginell Post & Hong Zan & Paolo Casali, 2022. "Rad52 mediates class-switch DNA recombination to IgD," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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