Curiouser and curiouser: the role(s) of AID expression in self-tolerance

Aicda is crucial for antibody diversification by mediating Ig class-switch recombination, V(D)J hypermutation (SHM) and, in some species, gene conversion. Recently, evidence has accumulated to show that Aicda is expressed during B-cell development and that this expression in some unknown way, mediates tolerance in immature and transitional B cells. In this issue of the European Journal of Immunology, Umiker et al. [Eur. J. Immunol. 2014. 44: 3093-3108] show that enforced expression of Aicda during early B-cell development is associated with self-tolerance. Curiously, constitutive Aicda expression that begins early in B cells suppresses the generation of autoreactive IgM but promotes the expression of self-reactive IgG. In contrast, when Aicda is activated later in B-cell development, self-reactive IgM is abundant but IgG is not. These observations suggest pathways for self-tolerance that have been little explored.