Activation-induced deaminase (AID) is a B-cell specific enzyme required for initiating the mechanisms of affinity maturation and isotype switching of antibodies. AID functions by deaminating cytosine to uracil in DNA, which initiates a cascade of events resulting in mutations and strand breaks in the immunoglobulin loci. There is an intricate interplay between faithful DNA repair and mutagenic DNA repair during somatic hypermutation, in that some proteins from accurate repair pathways are also involved in mutagenesis. We have found that one protein, XRCC1, is necessary for faithful repair, and in its absence, the mutation frequency goes up. In addition, after immunization, IgM memory cells outnumber and outlive their traditional IgG counterparts, indicating that these cells should be targeted for vaccination efforts.
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