Browsing by Author "Debre, Marianne"

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    Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans
    (Natl Acad Sciences, 2011-07-12) Meyers, Greta; Ng, Yen-Shing; Bannock, Jason M.; Lavoie, Aubert; Walter, Jolan E.; Notarangelo, Luigi D.; Kılıç, Sara S.; Aksu, Guzide; Debre, Marianne; Rieux-Laucat, Frederic; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Durandy, Anne; Meffre, Eric; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.; AAH-1658-2021
    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.