International Immunology Advance Access originally published online on November 15, 2005
International Immunology 2006 18(1):41-47; doi:10.1093/intimm/dxh347
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID
1 Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-Ku, Kyoto 606-8501, Japan
2 Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G-2E9, Canada
3 Department of Evolutionary Genetics, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-Ku, Kyoto 606-8501, Japan
Correspondence to: M. Muramatsu; E-mail: muramatu{at}mfour.med.kyoto-u.ac.jp
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.
Keywords: APOBEC-1, B cells, class switch recombination, immunoglobulin gene, somatic hypermutation
Transmitting editor: T. Watanabe
* These authors contributed equally to this study.
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
D. Roy and M. R. Lieber G Clustering Is Important for the Initiation of Transcription-Induced R-Loops In Vitro, whereas High G Density without Clustering Is Sufficient Thereafter Mol. Cell. Biol., June 1, 2009; 29(11): 3124 - 3133. [Abstract] [Full Text] [PDF] |
||||
![]() |
U. Basu, A. Franklin, and F. W Alt Post-translational regulation of activation-induced cytidine deaminase Phil Trans R Soc B, March 12, 2009; 364(1517): 667 - 673. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. McBride, A. Gazumyan, E. M. Woo, T. A. Schwickert, B. T. Chait, and M. C. Nussenzweig Regulation of class switch recombination and somatic mutation by AID phosphorylation J. Exp. Med., October 27, 2008; 205(11): 2585 - 2594. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Pham, M. B. Smolka, P. Calabrese, A. Landolph, K. Zhang, H. Zhou, and M. F. Goodman Impact of Phosphorylation and Phosphorylation-null Mutants on the Activity and Deamination Specificity of Activation-induced Cytidine Deaminase J. Biol. Chem., June 20, 2008; 283(25): 17428 - 17439. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Roy, K. Yu, and M. R. Lieber Mechanism of R-Loop Formation at Immunoglobulin Class Switch Sequences Mol. Cell. Biol., January 1, 2008; 28(1): 50 - 60. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Larijani and A. Martin Single-Stranded DNA Structure and Positional Context of the Target Cytidine Determine the Enzymatic Efficiency of AID Mol. Cell. Biol., December 1, 2007; 27(23): 8038 - 8048. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Chatterji, S. Unniraman, K. M. McBride, and D. G. Schatz Role of Activation-Induced Deaminase Protein Kinase A Phosphorylation Sites in Ig Gene Conversion and Somatic Hypermutation J. Immunol., October 15, 2007; 179(8): 5274 - 5280. [Abstract] [Full Text] [PDF] |
||||
![]() |
F.-T. Huang, K. Yu, B. B. Balter, E. Selsing, Z. Oruc, A. A. Khamlichi, C.-L. Hsieh, and M. R. Lieber Sequence Dependence of Chromosomal R-Loops at the Immunoglobulin Heavy-Chain S{micro} Class Switch Region Mol. Cell. Biol., August 15, 2007; 27(16): 5921 - 5932. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Larijani, A. P. Petrov, O. Kolenchenko, M. Berru, S. N. Krylov, and A. Martin AID Associates with Single-Stranded DNA with High Affinity and a Long Complex Half-Life in a Sequence-Independent Manner Mol. Cell. Biol., January 1, 2007; 27(1): 20 - 30. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. T. Ichikawa, M. P. Sowden, A. T. Torelli, J. Bachl, P. Huang, G. S. C. Dance, S. H. Marr, J. Robert, J. E. Wedekind, H. C. Smith, et al. Structural Phylogenetic Analysis of Activation-Induced Deaminase Function J. Immunol., July 1, 2006; 177(1): 355 - 361. [Abstract] [Full Text] [PDF] |
||||




