CSR is an intra-chromosomal deletion in antigen-stimulated B cells that allows Ig isotype switching from IgM/IgD to IgG, IgA or IgE. Failure of CSR leads to hyper-IgM syndrome. Dysregulation of CSR contributes to oncogenic chromosomal translocations frequently observed in B cell lymphomas. CSR is directed by large repetitive DNA regions (2~12kb) that lack extensive homology or conserved signal sequences. Another process also occurring in stimulated B cells is somatic hypermutation (SHM), which mutates the Ig variable regions to allow Ig affinity maturation. Like CSR, defective SHM leads to immunodeficiency, and aberrant targeting of SHM to non-Ig genes can produce oncogene mutations or chromosomal translocations in various types of B cell malignancies. Both SHM and CSR are initiated by a lymphoid specific factor called activation-induced cytidine deaminase (AID) that catalyzes DNA cytosine deamination at Ig variable and switch regions, respectively. AID is a small protein that shares homology to a large family of polynucleotide cytidine deaminases. Members of this family have diverse functions in RNA editing, gene conversion, Ig diversification, and host defense against retroviral infections.