Protein kinase Cδ is essential for the IgG response against T cell-independent type 2 antigens and commensal bacteria

  1. Saori Fukao
  2. Kei Haniuda
  3. Hiromasa Tamaki
  4. Daisuke Kitamura  Is a corresponding author
  1. Research Institute for Biomedical Sciences, Tokyo University of Science, Japan

Abstract

Antigens (Ags) with multivalent and repetitive structure elicit IgG production in a T cell-independent manner. However, the mechanisms by which such T cell-independent type-2 (TI-2) Ags induce IgG responses remain obscure. Here we report that BCR engagement with a TI-2 Ag but not with a T cell-dependent (TD) Ag was able to induce the transcription of Aicda encoding activation-induced cytidine deaminase (AID) and efficient class switching to IgG3 upon co-stimulation with IL-1 or IFN-α in mouse B cells. TI-2 Ags strongly induced the phosphorylation of protein kinase C (PKC)δ and PKCδ mediated the Aicda transcription through the induction of BATF, the key transcriptional regulator of Aicda. In PKCδ-deficient mice, production of IgG was intact against TD Ag but abrogated against typical TI-2 Ags as well as commensal bacteria, and experimental disruption of the gut epithelial barrier resulted in fatal bacteremia. Thus, our results have revealed novel molecular requirements for class-switching in the TI-2 response and highlighted its importance in homeostatic commensal-specific IgG production.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1-6, and figure supplements for Figures 1-3 and 5.

Article and author information

Author details

  1. Saori Fukao

    Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Kei Haniuda

    Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Hiromasa Tamaki

    Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Daisuke Kitamura

    Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan
    For correspondence
    kitamura@rs.tus.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5195-0474

Funding

Japan Society for the Promotion of Science (Grant-in-Aid for Early-Career Scientists,19K16700)

  • Saori Fukao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All mice were maintained in the Tokyo University of Science (TUS) mouse facility under specific pathogen-free conditions. Mouse procedures were performed under protocols approved by the TUS Animal Care and Use Committee (Approval No.: S19017, S20011).

Reviewing Editor

  1. Tomohiro Kurosaki, Osaka University, Japan

Publication history

  1. Received: July 12, 2021
  2. Preprint posted: July 20, 2021 (view preprint)
  3. Accepted: October 21, 2021
  4. Accepted Manuscript published: October 25, 2021 (version 1)
  5. Version of Record published: November 23, 2021 (version 2)

Copyright

© 2021, Fukao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Saori Fukao
  2. Kei Haniuda
  3. Hiromasa Tamaki
  4. Daisuke Kitamura
(2021)
Protein kinase Cδ is essential for the IgG response against T cell-independent type 2 antigens and commensal bacteria
eLife 10:e72116.
https://doi.org/10.7554/eLife.72116

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