Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells

  1. Fernando Y Maeda
  2. Jurriaan JH van Haaren
  3. David B Langley
  4. Daniel Christ
  5. Norma W Andrews  Is a corresponding author
  6. Wenxia Song  Is a corresponding author
  1. University of Maryland, United States
  2. Garvan Institute of Medical Research, Australia

Abstract

B-cell receptor (BCR)-mediated antigen internalization and presentation are essential for humoral memory immune responses. Antigen encountered by B-cells is often tightly associated with the surface of pathogens and/or antigen-presenting cells. Internalization of such antigens requires myosin-mediated traction forces and extracellular release of lysosomal enzymes, but the mechanism triggering lysosomal exocytosis is unknown. Here we show that BCR-mediated recognition of antigen tethered to beads, to planar lipid-bilayers or expressed on cell surfaces causes localized plasma membrane (PM) permeabilization, a process that requires BCR signaling and non-muscle myosin II activity. B-cell permeabilization triggers PM repair responses involving lysosomal exocytosis, and B-cells permeabilized by surface-associated antigen internalize more antigen than cells that remain intact. Higher affinity antigens cause more B-cell permeabilization and lysosomal exocytosis and are more efficiently presented to T-cells. Thus, PM permeabilization by surface-associated antigen triggers a lysosome-mediated B-cell resealing response, providing the extracellular hydrolases that facilitate antigen internalization and presentation.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Fernando Y Maeda

    Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jurriaan JH van Haaren

    Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David B Langley

    Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Christ

    Immunology, Garvan Institute of Medical Research, Darlinghurst/Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Norma W Andrews

    Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
    For correspondence
    andrewsn@umd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0611-2412
  6. Wenxia Song

    Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States
    For correspondence
    wenxsong@umd.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (R01 GM064625)

  • Norma W Andrews

National Institutes of Health (R01 GM064625)

  • Wenxia Song

National Institutes of Health (T32 GM080201)

  • Jurriaan JH van Haaren

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#R-JAN-18-02) of the University of Maryland. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Maryland on January 11, 2018 .

Reviewing Editor

  1. Michael L Dustin, University of Oxford, United Kingdom

Publication history

  1. Preprint posted: July 25, 2020 (view preprint)
  2. Received: January 28, 2021
  3. Accepted: October 26, 2021
  4. Accepted Manuscript published: October 27, 2021 (version 1)
  5. Version of Record published: November 12, 2021 (version 2)

Copyright

© 2021, Maeda 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. Fernando Y Maeda
  2. Jurriaan JH van Haaren
  3. David B Langley
  4. Daniel Christ
  5. Norma W Andrews
  6. Wenxia Song
(2021)
Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells
eLife 10:e66984.
https://doi.org/10.7554/eLife.66984

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