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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
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    References listed on IDEAS

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    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.
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