Class switch recombination (CSR) is a process by which B cells change the class of antibodies they produce in response to antigen stimulation and costimulatory signals. This process involves a unique type of intrachromosomal deletion recombination within special G-rich tandem repeated DNA sequences called switch (S) regions, located upstream of each heavy chain constant (CH) region gene, except for Cδ. The recombination is initiated by the B cell-specific activation-induced cytidine deaminase (AID), which deaminates cytosines in both the donor and acceptor S regions. AID activity converts several dC bases to dU bases in each S region, and the dU bases are then excised by the uracil DNA glycosylase UNG; the resulting abasic sites are nicked by apurinic/apyrimidinic endonuclease (APE). AID attacks both strands of transcriptionally active S regions, but how transcription promotes AID targeting is not entirely clear. Mismatch repair proteins are then involved in converting the resulting single-strand DNA breaks to double-strand breaks with DNA ends appropriate for end-joining recombination. Proteins required for the subsequent S-S recombination include DNA-PK, ATM, Mre11-Rad50-Nbs1, γH2AX, 53BP1, Mdc1, and XRCC4-ligase IV. These proteins are important for faithful joining of S regions, and in their absence aberrant recombination and chromosomal translocations involving S regions occur. CSR and somatic hypermutation (SHM) are initiated by AID, which converts cytosines in S regions and Ig variable regions to uracils by deamination. Subsequent repair of the dU residues leads to single-strand DNA breaks (SSBs) that must be converted to double-strand breaks (DSBs) within the donor Sμ region and within an acceptor Sx region, to initiate the process of intrachromosomal DNA recombination. This review focuses mainly on the overall mechanism of CSR, which is discussed in the next section. Although there are interesting similarities and differences between CSR and SHM, we do not discuss them owing to space constraints. SHM is reviewed in another article in this volume by M.D. Scharff. Also, we do not extensively review all the information available about AID, as this protein is extensively discussed in the Scharff article and in several other reviews. B cells undergo antibody, or Ig, class switching in vivo after immunization or infection or upon appropriate activation in culture. Engagement of the CD40 receptor on B cells by CD154 (CD40L) or, specifically for mouse B cells, the Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS), provides crucial signaling for CSR. AID expression is induced in mouseClass switch recombination (CSR) is a process by which B cells change the class of antibodies they produce in response to antigen stimulation and costimulatory signals. This process involves a unique type of intrachromosomal deletion recombination within special G-rich tandem repeated DNA sequences called switch (S) regions, located upstream of each heavy chain constant (CH) region gene, except for Cδ. The recombination is initiated by the B cell-specific activation-induced cytidine deaminase (AID), which deaminates cytosines in both the donor and acceptor S regions. AID activity converts several dC bases to dU bases in each S region, and the dU bases are then excised by the uracil DNA glycosylase UNG; the resulting abasic sites are nicked by apurinic/apyrimidinic endonuclease (APE). AID attacks both strands of transcriptionally active S regions, but how transcription promotes AID targeting is not entirely clear. Mismatch repair proteins are then involved in converting the resulting single-strand DNA breaks to double-strand breaks with DNA ends appropriate for end-joining recombination. Proteins required for the subsequent S-S recombination include DNA-PK, ATM, Mre11-Rad50-Nbs1, γH2AX, 53BP1, Mdc1, and XRCC4-ligase IV. These proteins are important for faithful joining of S regions, and in their absence aberrant recombination and chromosomal translocations involving S regions occur. CSR and somatic hypermutation (SHM) are initiated by AID, which converts cytosines in S regions and Ig variable regions to uracils by deamination. Subsequent repair of the dU residues leads to single-strand DNA breaks (SSBs) that must be converted to double-strand breaks (DSBs) within the donor Sμ region and within an acceptor Sx region, to initiate the process of intrachromosomal DNA recombination. This review focuses mainly on the overall mechanism of CSR, which is discussed in the next section. Although there are interesting similarities and differences between CSR and SHM, we do not discuss them owing to space constraints. SHM is reviewed in another article in this volume by M.D. Scharff. Also, we do not extensively review all the information available about AID, as this protein is extensively discussed in the Scharff article and in several other reviews. B cells undergo antibody, or Ig, class switching in vivo after immunization or infection or upon appropriate activation in culture. Engagement of the CD40 receptor on B cells by CD154 (CD40L) or, specifically for mouse B cells, the Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS), provides crucial signaling for CSR. AID expression is induced in mouse