1. Immunology and Inflammation
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The quantity of CD40 signaling determines the differentiation of B cells into functionally distinct memory cell subsets

  1. Takuya Koike
  2. Koshi Harada
  3. Shu Horiuchi
  4. Daisuke Kitamura  Is a corresponding author
  1. Tokyo University of Science, Japan
Research Article
  • Cited 5
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Cite this article as: eLife 2019;8:e44245 doi: 10.7554/eLife.44245

Abstract

In mice, memory B (Bmem) cells can be divided into two subpopulations: CD80hi Bmem cells that preferentially differentiate into plasma cells and CD80lo Bmem cells that become germinal center (GC) B cells during a recall response. We demonstrate that these distinct responses can be B cell-intrinsic and essentially independent of B-cell receptor (BCR) isotypes. Furthermore, we found that development of CD80hi Bmem cells in the primary immune response requires follicular helper T cells, a relatively strong CD40 signal and a high affinity BCR on B cells, whereas development of CD80lo Bmem cells does not. Quantitative differences in CD40 stimulation were enough to recapitulate the distinct B cell fate decisions in an in vitro culture system. The quantity of CD40 signaling appears to be translated into NF-kB activation followed by BATF upregulation to promote Bmem cell differentiation from GC B cells.

Article and author information

Author details

  1. Takuya Koike

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

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

    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.noda.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 (16H05206)

  • Daisuke Kitamura

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 animal experiments were performed under protocols approved by the Animal Care and Use Committee of the Tokyo University of Science (Approval No.: S15021, S16019, S17004, S18018). All surgery was performed under Isoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Facundo D Batista, Ragon Institute of MGH, MIT and Harvard, United States

Publication history

  1. Received: December 9, 2018
  2. Accepted: June 14, 2019
  3. Accepted Manuscript published: June 21, 2019 (version 1)
  4. Version of Record published: July 17, 2019 (version 2)

Copyright

© 2019, Koike 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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