The article provides a comprehensive overview of the mechanism and regulation of class switch recombination (CSR) in mature B cells. CSR is a process where B cells switch from producing one antibody isotype to another in response to antigen stimulation and costimulatory signals. The process involves intrachromosomal deletional recombination within G-rich tandem repeated DNA sequences called switch (S) regions, located upstream of each heavy chain constant (C_H) region gene, except Cδ. The recombination is initiated by activation-induced cytidine deaminase (AID), which deaminates cytosines in the donor and acceptor S regions, converting them to uracils. These uracils are then excised by uracil DNA glycosylase (UNG) and the resulting abasic sites are nicked by apurinic/apyrimidinic endonuclease (APE). Mismatch repair proteins are involved in converting single-strand DNA breaks to double-strand breaks, which are then joined by proteins such as DNA-PK, ATM, Mre11-Rad50-Nbs1, γH2AX, 53BP1, Mdc1, and XRCC4-ligase IV. These proteins are crucial for faithful joining of S regions and their absence leads to aberrant recombination and chromosomal translocations. The article also discusses the regulation of CSR, including the role of germline (GL) transcripts, which direct AID to specific S regions and make them suitable substrates for AID activity. The transcription of GL transcripts is induced by various cytokines and signaling pathways, and their presence is essential for CSR to occur. Additionally, the article explores the involvement of R-loops, which are RNA-DNA hybrids formed at the Sμ region, in the targeting of AID to the Sμ region. Overall, the article provides a detailed understanding of the molecular mechanisms and regulatory factors involved in CSR, highlighting the importance of these processes in antibody class switching.The article provides a comprehensive overview of the mechanism and regulation of class switch recombination (CSR) in mature B cells. CSR is a process where B cells switch from producing one antibody isotype to another in response to antigen stimulation and costimulatory signals. The process involves intrachromosomal deletional recombination within G-rich tandem repeated DNA sequences called switch (S) regions, located upstream of each heavy chain constant (C_H) region gene, except Cδ. The recombination is initiated by activation-induced cytidine deaminase (AID), which deaminates cytosines in the donor and acceptor S regions, converting them to uracils. These uracils are then excised by uracil DNA glycosylase (UNG) and the resulting abasic sites are nicked by apurinic/apyrimidinic endonuclease (APE). Mismatch repair proteins are involved in converting single-strand DNA breaks to double-strand breaks, which are then joined by proteins such as DNA-PK, ATM, Mre11-Rad50-Nbs1, γH2AX, 53BP1, Mdc1, and XRCC4-ligase IV. These proteins are crucial for faithful joining of S regions and their absence leads to aberrant recombination and chromosomal translocations. The article also discusses the regulation of CSR, including the role of germline (GL) transcripts, which direct AID to specific S regions and make them suitable substrates for AID activity. The transcription of GL transcripts is induced by various cytokines and signaling pathways, and their presence is essential for CSR to occur. Additionally, the article explores the involvement of R-loops, which are RNA-DNA hybrids formed at the Sμ region, in the targeting of AID to the Sμ region. Overall, the article provides a detailed understanding of the molecular mechanisms and regulatory factors involved in CSR, highlighting the importance of these processes in antibody class switching.