Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans
Küçük Resim Yok
Tarih
2011
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Natl Acad Sciences
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Impaired immune functions leading to primary immunodeficiencies often correlate with paradoxical autoimmune complications; patients with hyper-IgM syndromes who are deficient in activation-induced cytidine deaminase (AID), which is required for classs-witch recombination and somatic hypermutation, are prone to develop autoimmune diseases. To investigate the impact of AID-deficiency on early B-cell tolerance checkpoints in humans, we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from AID-deficient patients. New emigrant/transitional and mature naive B cells from AID-deficient patients express an abnormal Ig repertoire and high frequencies of autoreactive antibodies, demonstrating that AID is required for the establishment of both central and peripheral B-cell tolerance. In addition, B-cell tolerance was further breached in AID-deficient patients as illustrated by the detection of anti-nuclear IgM antibodies in the serum of all patients. Thus, we identified a major and previously unsuspected role for AID in the removal of developing autoreactive B cells in humans.
Açıklama
Anahtar Kelimeler
Kaynak
Proceedings of the National Academy of Sciences of the United States of America
WoS Q Değeri
Q1
Scopus Q Değeri
N/A
Cilt
108
Sayı
28
