1. Immunology and Inflammation
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The activation of IgM- or isotype-switched IgG- and IgE-BCR exhibits distinct mechanical force sensitivity and threshold

  1. Zhengpeng Wan
  2. Xiangjun Chen
  3. Haodong Chen
  4. Qinghua Ji
  5. Yingjia Chen
  6. Jing Wang
  7. Yiyun Cao
  8. Fei Wang
  9. Jizhong Lou
  10. Zhuo Tang
  11. Wanli Liu  Is a corresponding author
  1. Tsinghua University, China
  2. Chinese Academy of Science, China
  3. Chinese Academy of Sciences, China
Research Article
  • Cited 43
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Cite this article as: eLife 2015;4:e06925 doi: 10.7554/eLife.06925

Abstract

B lymphocytes use B cell receptors (BCRs) to sense the physical features of the antigens. However, the sensitivity and threshold for the activation of BCRs resulting from the stimulation by mechanical forces are unknown. Here we addressed this question using a double-stranded DNA based tension gauge tether system serving as a predefined mechanical force gauge ranging from 12 to 56 pN. We observed that IgM-BCR activation is dependent on mechanical forces and exhibits a multi-threshold effect. In contrast, the activation of isotype-switched IgG- or IgE-BCR only requires a low threshold of less than 12 pN, providing an explanation for their rapid activation in response to antigen stimulation. Mechanistically, we found that the cytoplasmic tail of the IgG-BCR heavy chain is both required and sufficient to account for the low mechanical force threshold. These results defined the mechanical force sensitivity and threshold that are required to activate different isotyped BCRs.

Article and author information

Author details

  1. Zhengpeng Wan

    MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiangjun Chen

    MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Haodong Chen

    Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Qinghua Ji

    Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yingjia Chen

    MOE Key Laboratory of Protein Sciences, School of Life Science, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Jing Wang

    MOE Key Laboratory of Protein Sciences, School of Life Science, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Yiyun Cao

    MOE Key Laboratory of Protein Sciences, School of Life Science, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Fei Wang

    Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Jizhong Lou

    Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Zhuo Tang

    Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Wanli Liu

    MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    For correspondence
    liuwanli@biomed.tsinghua.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Ronald N Germain, National Institute of Allergy and Infectious Diseases, United States

Publication history

  1. Received: March 6, 2015
  2. Accepted: August 8, 2015
  3. Accepted Manuscript published: August 10, 2015 (version 1)
  4. Version of Record published: September 1, 2015 (version 2)

Copyright

© 2015, Wan 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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