DNA Repair during Class Switch Recombination

Abstract

B cells undergo secondary antibody diversification to elicit an effective humoral immune response. Secondary antibody diversification can generate different classes of antibodies, which mediate different effector functions, enabling the humoral response to be fine-tuned to the infection at hand. The process of producing different classes of antibodies is called class switch recombination (CSR), and it requires the generation and repair of double-stranded DNA breaks at the antibody heavy chain locus. These DNA breaks activate the DNA damage response (DDR) and DNA repair pathways. The DDR pathway elicited by CSR involves ATM, Mre11–Rad50–NBS1, γH2AX, MDC1, RNF8, RNF168, 53BP1, and Rif1. This pathway is important for protecting the DNA breaks from DNA end resection, and promoting long-range DNA end joining via the nonhomologous end joining (NHEJ) DNA repair mechanism. While NHEJ is the primary DNA repair mechanism used during CSR, microhomology-mediated end joining can also contribute to repairing the DNA breaks.