The AID enzyme induces class switch recombination in fibroblasts

Nature. 2002 Mar 21;416(6878):340-5. doi: 10.1038/nature727. Epub 2002 Mar 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • CD8 Antigens
  • Luminescent Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Green Fluorescent Proteins
  • DNA
  • Phosphotransferases (Alcohol Group Acceptor)
  • hygromycin-B kinase
  • Thymidine Kinase
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase