RRC ID 35959
Author Okazaki IM, Kinoshita K, Muramatsu M, Yoshikawa K, Honjo T.
Title The AID enzyme induces class switch recombination in fibroblasts.
Journal Nature
Abstract The switch of the immunoglobulin isotype from IgM to IgG, IgE or IgA is mediated by class switch recombination (CSR). CSR changes the immunoglobulin heavy chain constant region (CH) gene from Cmu to one of the other CH genes. Somatic hypermutation introduces massive numbers of point mutations in the immunoglobulin variable (V) region gene, giving rise to immunoglobulin with higher affinity. Activation-induced cytidine deaminase (AID), a putative RNA-editing cytidine deaminase, is expressed strictly in activated B cells and is indispensable in both CSR and somatic hypermutation. But the exact function of AID is unknown. Here we show that ectopic expression of AID induces CSR in an artificial switch construct in fibroblasts at a level comparable to that in stimulated B cells. Sequences around recombination junctions in the artificial substrate have features similar to endogenous CSR junctions. Furthermore, AID-induced CSR in fibroblasts is dependent on transcription of the target S region, as shown in endogenous CSR in B cells. The results show that AID is the only B-cell-specific factor required for initiation of the CSR reaction in the activated locus.
Volume 416(6878)
Pages 340-5
Published 2002-3-21
DOI 10.1038/nature727
PII nature727
PMID 11875397
MeSH 3T3 Cells Animals B-Lymphocytes / immunology B-Lymphocytes / physiology* Base Sequence CD8 Antigens / genetics Cytidine Deaminase / physiology* DNA Fibroblasts Green Fluorescent Proteins Immunoglobulin Class Switching / physiology* Luminescent Proteins / genetics Mice Molecular Sequence Data Phosphotransferases (Alcohol Group Acceptor) / genetics Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Recombination, Genetic Thymidine Kinase / genetics Trans-Activators Transcription, Genetic Transfection Tumor Cells, Cultured
IF 42.779
Times Cited 196
DNA material pSCI (mu alpha) (RDB02861)