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.

du Pre, M.f., Blazevski, J., Dewan, A.e., Stamnaes, J., Kanduri, C., Sandve, G.k., et al. (2020). B cell tolerance and antibody production to the celiac disease autoantigen transglutaminase 2. THE JOURNAL OF EXPERIMENTAL MEDICINE, 217(2) [10.1084/jem.20190860].

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

Melino, Gennaro;
2020-01-01

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
du Pre, M.f., Blazevski, J., Dewan, A.e., Stamnaes, J., Kanduri, C., Sandve, G.k., et al. (2020). B cell tolerance and antibody production to the celiac disease autoantigen transglutaminase 2. THE JOURNAL OF EXPERIMENTAL MEDICINE, 217(2) [10.1084/jem.20190860].
du Pre, Mf; Blazevski, J; Dewan, Ae; Stamnaes, J; Kanduri, C; Sandve, Gk; Johannesen, Mk; Lindstad, Cb; Hnida, K; Fugger, L; Melino, G; Qiao, S; Sollid, Lm
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/238785
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