| 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
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| DNA material |
pSCI (mu
alpha) (RDB02861) |
