This review discusses evolution of the process of Ig heavy chain class switching, relating it to the first appearance of somatic hypermutation (SHM) of variable region genes. First, we discuss recent findings on the mechanism of class switch recombination (CSR) in mice and humans, and then review the mechanisms of expression of Ig heavy chain isotypes from fishes to mammals. Importantly, activation-induced cytidine deaminase (AID), which is essential for CSR and somatic hypermutation, is found in fishes. Although at least some fishes are likely to undergo SHM, CSR is highly unlikely to occur in this group. We discuss the first appearance of CSR in amphibians and how it differs in birds and mammals.

• AI23283/AI/NIAID NIH HHS/United States
• HG02526/HG/NHGRI NIH HHS/United States