Rabbit Anti-Human AICDA (N-terminal) Polyclonal antibody

B-1a cells are innate-like B-lymphocytes producing natural antibodies. Activationinduced cytidine deaminase (AID), a product of the Aicda gene, plays a central role in class-switch recombination and somatic hypermutation in B cells. Although a role for Aicda in B-1a cells has been suggested on the basis of experiments with knock out (KO) mice, whether B-1a cells express Aicda, and if so, which B-1a cell subpopulation expresses Aicda, remains unknown. Here, we demonstrate that B-1 cells express Aicda, but at a level below that expressed by germinal center (GC) B cells. We previously reported that B-1a cells can be subdivided based on CD25 expression. We show here that B-1a cell Aicda expression is concentrated in the CD25(+) B-1a cell subpopulation. These results suggest the possibility that previous studies of memory B cells identified on the basis of Aicda expression may have inadvertently included an unknown number of CD25(+) B-1a cells. Although B-1a cells develop normally in the absence of Aicda, a competitive reconstitution assay reveals enhanced vigor for AID KO B-1a cell bone marrow (BM) progenitors, as compared with wild-type BM B-1 cell progenitors. These results suggest that AID inhibits the development of B-1a cells from BM B-1 cell progenitors in a competitive environment.

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.