Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans

G Meyers, YS Ng, JM Bannock… - Proceedings of the …, 2011 - National Acad Sciences
G Meyers, YS Ng, JM Bannock, A Lavoie, JE Walter, LD Notarangelo, SS Kilic, G Aksu
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
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 class-switch
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 …
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 class-switch 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.
National Acad Sciences