With all the uncertainty of COVID-19, we hope you are safe and in good health. Ozgene is still here to meet your research needs.

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

 Back to publications

2020

J Exp Med. 2020 Feb 3;217(2). pii: e20190860. doi: 10.1084/jem.20190860.

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

MF du Pré;J Blazevski;AE Dewan;J Stamnaes;C Kanduri;GK Sandve;MK Johannesen;CB Lindstad;K Hnida;L Fugger;G Melino;SW Qiao;LM Sollid

University of Oslo, Oslo, Norway. Oslo University Hospital, Oslo, Norway. University of Oxford, Oxford, UK. University of Rome "Tor Vergata", Rome, Italy.

Service type: Knock-in mice

Abstract

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.

View Publication