IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42541-7.html
   My bibliography  Save this article

Antigen presentation by B cells enables epitope spreading across an MHC barrier

Author

Listed:
  • Cecilia Fahlquist-Hagert

    (Aarhus University)

  • Thomas R. Wittenborn

    (Aarhus University)

  • Ewa Terczyńska-Dyla

    (Aarhus University)

  • Kristian Savstrup Kastberg

    (Aarhus University)

  • Emily Yang

    (Stanford University)

  • Alysa Nicole Rallistan

    (Stanford University)

  • Quinton Raymond Markett

    (Stanford University)

  • Gudrun Winther

    (Aarhus University)

  • Sofie Fonager

    (Aarhus University)

  • Lasse F. Voss

    (Aarhus University
    Technical University of Denmark)

  • Mathias K. Pedersen

    (Aarhus University)

  • Nina Campen

    (Aarhus University
    Radboud University Medical Center)

  • Alexey Ferapontov

    (Aarhus University
    Aarhus University)

  • Lisbeth Jensen

    (Aarhus University)

  • Jinrong Huang

    (Aarhus University
    Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen)

  • John D. Nieland

    (Aalborg University)

  • Cees E. Poel

    (Boston Children’s Hospital
    Dragonfly Therapeutics)

  • Johan Palmfeldt

    (Aarhus University)

  • Michael C. Carroll

    (Boston Children’s Hospital)

  • Paul J. Utz

    (Stanford University
    Stanford University School of Medicine)

  • Yonglun Luo

    (Aarhus University
    Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen
    Aarhus University Hospital)

  • Lin Lin

    (Aarhus University
    Aarhus University Hospital)

  • Søren E. Degn

    (Aarhus University
    Aarhus University)

Abstract

Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.

Suggested Citation

  • Cecilia Fahlquist-Hagert & Thomas R. Wittenborn & Ewa Terczyńska-Dyla & Kristian Savstrup Kastberg & Emily Yang & Alysa Nicole Rallistan & Quinton Raymond Markett & Gudrun Winther & Sofie Fonager & La, 2023. "Antigen presentation by B cells enables epitope spreading across an MHC barrier," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42541-7
    DOI: 10.1038/s41467-023-42541-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42541-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-42541-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Tanja A. Schwickert & Randall L. Lindquist & Guy Shakhar & Geulah Livshits & Dimitris Skokos & Marie H. Kosco-Vilbois & Michael L. Dustin & Michel C. Nussenzweig, 2007. "In vivo imaging of germinal centres reveals a dynamic open structure," Nature, Nature, vol. 446(7131), pages 83-87, March.
    2. Sarah Esther Chang & Allan Feng & Wenzhao Meng & Sokratis A. Apostolidis & Elisabeth Mack & Maja Artandi & Linda Barman & Kate Bennett & Saborni Chakraborty & Iris Chang & Peggie Cheung & Sharon Chint, 2021. "New-onset IgG autoantibodies in hospitalized patients with COVID-19," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hideki Ogura & Jin Gohda & Xiuyuan Lu & Mizuki Yamamoto & Yoshio Takesue & Aoi Son & Sadayuki Doi & Kazuyuki Matsushita & Fumitaka Isobe & Yoshihiro Fukuda & Tai-Ping Huang & Takamasa Ueno & Naomi Mam, 2022. "Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Otavio Cabral-Marques & Gilad Halpert & Lena F. Schimke & Yuri Ostrinski & Aristo Vojdani & Gabriela Crispim Baiocchi & Paula Paccielli Freire & Igor Salerno Filgueiras & Israel Zyskind & Miriam T. La, 2022. "Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Jakob Ankerhold & Sebastian Giese & Philipp Kolb & Andrea Maul-Pavicic & Reinhard E. Voll & Nathalie Göppert & Kevin Ciminski & Clemens Kreutz & Achim Lother & Ulrich Salzer & Wolfgang Bildl & Tim Wel, 2022. "Circulating multimeric immune complexes contribute to immunopathology in COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Al Ozonoff & Naresh Doni Jayavelu & Shanshan Liu & Esther Melamed & Carly E. Milliren & Jingjing Qi & Linda N. Geng & Grace A. McComsey & Charles B. Cairns & Lindsey R. Baden & Joanna Schaenman & Albe, 2024. "Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Renske M A Vroomans & Athanasius F M Marée & Rob J de Boer & Joost B Beltman, 2012. "Chemotactic Migration of T Cells towards Dendritic Cells Promotes the Detection of Rare Antigens," PLOS Computational Biology, Public Library of Science, vol. 8(11), pages 1-13, November.
    6. Jillian R. Jaycox & Carolina Lucas & Inci Yildirim & Yile Dai & Eric Y. Wang & Valter Monteiro & Sandra Lord & Jeffrey Carlin & Mariko Kita & Jane H. Buckner & Shuangge Ma & Melissa Campbell & Albert , 2023. "SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    7. Chung Il Park & Seungah Choe & Woorim Lee & Wonjae Choi & Miso Kim & Hong Min Seung & Yoon Young Kim, 2023. "Ultrasonic barrier-through imaging by Fabry-Perot resonance-tailoring panel," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    8. Thomas Hu & Mayar Allam & Shuangyi Cai & Walter Henderson & Brian Yueh & Aybuke Garipcan & Anton V. Ievlev & Maryam Afkarian & Semir Beyaz & Ahmet F. Coskun, 2023. "Single-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. Liat Stoler-Barak & Ethan Harris & Ayelet Peres & Hadas Hezroni & Mirela Kuka & Pietro Lucia & Amalie Grenov & Neta Gurwicz & Meital Kupervaser & Bon Ham Yip & Matteo Iannacone & Gur Yaari & John D. C, 2023. "B cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Manina M. Etter & Tomás A. Martins & Laila Kulsvehagen & Elisabeth Pössnecker & Wandrille Duchemin & Sabrina Hogan & Gretel Sanabria-Diaz & Jannis Müller & Alessio Chiappini & Jonathan Rychen & Noëmi , 2022. "Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42541-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.