Targeting of AID to antibody variable (V) regions results in somatic hypermutation, whereas its recruitment to switch (S) regions leads to class-switch recombination. Yeap et al. find that the mechanism by which variable and switch regions recruit AID essentially is the same but that the two regions differ in the density of double-stranded DNA breaks that are generated. These lead to either poi...

We generated MRL/lpr mice deficient in activation-induced deaminase (AID). Because AID is required for Ig hypermutation and class switch recombination, these mice lack hypermutated IgG Abs. Unlike their AID wild-type littermates, AID-deficient MRL/lpr mice not only lacked autoreactive IgG Abs but also experienced a dramatic increase in the levels of autoreactive IgM. This phenotype in AID-defic...

Although relatively rare, primary immunodeficiency diseases (PIDs) provide an excellent window into the functioning of the immune system. In the late 1960s, observations on these diseases, with their associated infections and genetics, bisected the immune system into humoral immunity and cell-mediated immunity. These diseases also represent a challenge in their diagnosis and treatment. Beginnin...

Primary antibody deficiencies (PAD) form the largest group of inherited disorders of the immune system. They are characterized by a marked reduction or absence of serum immunglobulins (Ig) and/or a poor response to vaccination due to disturbed B-cell differentiation. PAD can be divided in agammaglobulinemia, Ig class switch recombination defects (formerly called hyper IgM syndromes), and idiopa...

The generation of high-affinity antibodies requires somatic hypermutation (SHM) and class switch recombination (CSR) at the immunoglobulin (Ig) locus. Both processes are triggered by activation-induced cytidine deaminase (AID) and require UNG-encoded uracil-DNA glycosylase. AID has been suggested to function as an mRNA editing deaminase or as a single-strand DNA deaminase. In the latter model, ...

Because of its susceptibility to apoptosis on Ag receptor cross-linking, cells of the mouse cell line WEHI-231 have been classified as immature B cells. Surprisingly, however, the cell line expresses activation-induced cytidine deaminase, the enzyme that mediates hypermutation and Ig class switch recombination in activated B cells. Although both cDNA sequence and protein expression of activatio...

Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed Cμ (IgM) constant regions (C(H)) exons with downstream C(H) exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from Cμ to Cγ1 (IgG1) and Cε (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although Cε CSR can occur directly from Cμ, most mature pe...