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Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection

Author

Listed:
  • Yuta Asano

    (Section of Rheumatology and The Knapp Center for Lupus and Immunology Research, Department of Medicine, The University of Chicago)

  • Joe Daccache

    (Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School)

  • Dharmendra Jain

    (Section of Transplant, Department of Surgery, The University of Chicago)

  • Kichul Ko

    (Section of Rheumatology and The Knapp Center for Lupus and Immunology Research, Department of Medicine, The University of Chicago)

  • Andrew Kinloch

    (Section of Rheumatology and The Knapp Center for Lupus and Immunology Research, Department of Medicine, The University of Chicago)

  • Margaret Veselits

    (Section of Rheumatology and The Knapp Center for Lupus and Immunology Research, Department of Medicine, The University of Chicago)

  • Donald Wolfgeher

    (The University of Chicago)

  • Anthony Chang

    (The University of Chicago)

  • Michelle Josephson

    (Section of Nephrology, Department of Medicine, The University of Chicago)

  • Patrick Cunningham

    (Section of Nephrology, Department of Medicine, The University of Chicago)

  • Anat Tambur

    (Transplant Immunology Laboratory, Northwestern University)

  • Aly A. Khan

    (The University of Chicago)

  • Shiv Pillai

    (Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Department of Medicine, Harvard Medical School)

  • Anita S. Chong

    (Section of Transplant, Department of Surgery, The University of Chicago)

  • Marcus R. Clark

    (Section of Rheumatology and The Knapp Center for Lupus and Immunology Research, Department of Medicine, The University of Chicago)

Abstract

Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.

Suggested Citation

  • Yuta Asano & Joe Daccache & Dharmendra Jain & Kichul Ko & Andrew Kinloch & Margaret Veselits & Donald Wolfgeher & Anthony Chang & Michelle Josephson & Patrick Cunningham & Anat Tambur & Aly A. Khan & , 2021. "Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24615-6
    DOI: 10.1038/s41467-021-24615-6
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