Lars Henrik Fugger

B cell tolerance and antibody production to the celiac disease autoantigen transglutaminase 2

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DOI

  • M Fleur du Pré, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
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  • Jana Blazevski, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
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  • Alisa E Dewan, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
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  • Jorunn Stamnaes, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
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  • Chakravarthi Kanduri, Department of Gynaecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Institute for Cancer Genetics and Informatics, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Faculty of Medicine, University of Oslo, Oslo, Norway.
  • ,
  • Geir Kjetil Sandve, Department of Gynaecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Institute for Cancer Genetics and Informatics, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Faculty of Medicine, University of Oslo, Oslo, Norway.
  • ,
  • Marie K Johannesen, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
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  • Christian B Lindstad, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
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  • Kathrin Hnida, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
  • ,
  • Lars Fugger
  • Gerry Melino, Department of Experimental Medicine, TOR, University of Rome "Tor Vergata", Rome, Italy.
  • ,
  • Shuo-Wang Qiao, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.
  • ,
  • Ludvig M Sollid, Department of Immunology and Transfusion Medicine, Oslo University Hospital, Oslo, Norway.

Autoantibodies to transglutaminase 2 (TG2) are hallmarks of celiac disease. To address B cell tolerance and autoantibody formation to TG2, we generated immunoglobulin knock-in (Ig KI) mice that express a prototypical celiac patient-derived anti-TG2 B cell receptor equally reactive to human and mouse TG2. We studied B cell development in the presence/absence of autoantigen by crossing the Ig KI mice to Tgm2-/- mice. Autoreactive B cells in Tgm2+/+ mice were indistinguishable from their naive counterparts in Tgm2-/- mice with no signs of clonal deletion, receptor editing, or B cell anergy. The autoreactive B cells appeared ignorant to their antigen, and they produced autoantibodies when provided T cell help. The findings lend credence to a model of celiac disease where gluten-reactive T cells provide help to autoreactive TG2-specific B cells by involvement of gluten-TG2 complexes, and they outline a general mechanism of autoimmunity with autoantibodies being produced by ignorant B cells on provision of T cell help.

Original languageEnglish
Article numbere20190860
JournalThe Journal of Experimental Medicine
Volume217
Issue2
ISSN0022-1007
DOIs
Publication statusPublished - 3 Feb 2020

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