The First B-Cell Tolerance Checkpoint in Mice and Humans: Control by AID.

Authors: Kuraoka M, Meffre E, Kelsoe G Abstract Activation-induced cytidine deaminase (AID) expression in the germinal center response drives the immunoglobulin class-switch recombination and V(D)J hypermutation necessary for efficacious, high-affinity antibody responses. That AID is expressed in developing lymphocytes is less well known, but represents an evolutionarily conserved pattern of lymphocyte development that is represented in all vertebrate species. Here we review the role of early, developmentally regulated AID expression in mice and humans and its role in establishing the first B-cell tolerance checkpoint. This newly recognized component of central tolerance requires coordinate signaling by poly- or autoreactive B-cell antigen receptors and endosomal Toll-like receptor...

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