Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID.
Following activation of mammalian B cells, class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the functions of the expressed antibodies. Activation-induced cytidine deaminase (AID) is the only known B cell-specific protein required for inducing CSR and SHM in mammals. Lower vertebrates have an AID homologue, and there is some evidence of SHM in vivo. However there is no evidence of CSR in the cartilaginous or bony fishes, and this may be due in part to a lack of cis-elements in the IgH gene that are the normal targets of AID-mediated recombination. We have tested whether bony fish (zebrafish and catfish) AID can mediate CSR and SHM in mammalian cells. As expected, ectopic expression of fish AID in mouse fibroblasts resulted in mutations in an introduced SHM reporter gene, indicating that fish AID can mediate SHM. Unexpectedly, expression of fish AID in mouse AID-/- B cells induced surface IgG expression as well as switched transcripts from Ig gene loci, clearly indicating that the fish AID protein can mediate CSR, at least in mouse cells. These results suggest that the AID protein acquired the ability to mediate CSR before the IgH locus evolved the additional exon clusters and switch regions that are the targets of recombination. We discuss how pleiotropic functions of specific domains within the AID protein may have facilitated the early evolution of CSR in lower vertebrates.
Wakae
Koshou
K
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-Ku, Kyoto 606-8501, Japan.
Magor
Brad G
BG
Saunders
Holly
H
Nagaoka
Hitoshi
H
Kawamura
Akemi
A
Kinoshita
Kazuo
K
Honjo
Tasuku
T
Muramatsu
Masamichi
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002645:Chickens; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology*; D019143:Evolution, Molecular; D007059:Ictaluridae / Q000235:genetics / Q000276:immunology*; D051379:Mice; D017434:Protein Structure, Tertiary / Q000235:genetics; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology*; D015027:Zebrafish / Q000235:genetics / Q000276:immunology
D003564:Cytidine Deaminase