摘要：

Antigen-stimulated B-cells can undergo immunoglobulin-heavy (IgH) class switch recombination (CSR) to change the expressed IgH constant (C) region and thereby diversify antibody effector functions. Activation-induced cytidine deaminase (AID), a single-strand DNA-specific cytidine deaminase, initiates both CSR and the related variable region somatic hypermutation process. During CSR, AID is targeted to long repetitive IgH switch (S) regions that precede exons ("C H s") that encode particular IgH C regions. Switch region deamination products in a donor and acceptor S region are channeled into DNA double-strand breaks (DSBs) that are ligated by general cellular DSB repair pathways to fuse the two S regions and change antibody class by replacing the expressed C H with a different one. We discuss the mechanism of CSR with a focus on how factors target AID to S region substrates, and how DNA repair pathways efficiently fuse together DSBs in two different S regions without causing genomic instability.

展开