| First Author | du Pré MF | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 2 | PubMed ID | 31727780 |
| Mgi Jnum | J:285062 | Mgi Id | MGI:6392729 |
| Doi | 10.1084/jem.20190860 | Citation | du Pre MF, et al. (2020) B cell tolerance and antibody production to the celiac disease autoantigen transglutaminase 2. J Exp Med 217(2) |
| abstractText | 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. |
