A novel role for activation-induced cytidinedeaminase: central B-cell tolerance.

摘要

Activation-induced cytidine deaminase (AID) initiates immunoglobulin gene (Ig) hypermutation (SHM), class-switch recombination (CSR) and gene conversion. These processes are crucial for effective humoral immunity; in germinal centers (GC), SHM drives Darwinian selection for B cells carrying higher affinity B-cell receptors (BCR), and CSR permits the generation of distinct classes of antibodies that possess different physiologic activities.In mice and humans, physiologically significant AID expression has been thought to be restricted to GC B cells. Nonetheless, AID expression, SHM and CSR are also present in mature, non-GC B cells. In addition, lower levels of AID message, CSR and SHM have been observed in mouse immature and tran-sitional-l (immature/T1) B cells and in human fetal liver. The significance of low-level AID expression in developing B cells is controversial, though similar or even lower levels of AID have been shown to play a significant role in the maintenance of totipotency in embryonic stem cells.