NF-kappaB family of transcription factor facilitates gene conversion in chicken B cells

Activation-induced cytidine deaminase (AID) is critical for immunoglobulin (Ig) diversification in B cells. The majority of evidence supports the model that AID modifies Ig genes at the DNA level by deaminating cytosines into uracils. The mutagenic activity is largely restricted to Ig genes to avoid genomic damage in general, but the underlying mechanism is not understood. We addressed this question in chicken B cell line DT40. We characterized a regulatory region within the Iglambda locus. This regulatory region is important for AID-mediated gene conversion at the Iglambda locus, and is capable of targeting AID activity to ectopic loci. This regulatory region contains binding sites for transcription factors NF-kappaB, Mef2 and octamer binding proteins. Mutation of these binding sites or ablation of NF-kappaB family member, p50 or c-Rel, impairs the AID targeting function of this regulatory region. These results suggest that NF-kappaB family of transcription factors contribute to AID-mediated gene conversion.