Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice

Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1616-20. doi: 10.1073/pnas.0610732104. Epub 2007 Jan 24.

Abstract

Activation-induced cytidine deaminase (AID), which is essential to both class switch recombination and somatic hypermutation of the Ig gene, is expressed in many types of human B cell lymphoma/leukemia. AID is a potent mutator because it is involved in DNA breakage not only of Ig but also of other genes, including proto-oncogenes. Recent studies suggest that AID is required for chromosomal translocation involving cmyc and Ig loci. However, it is unclear whether AID plays other roles in tumorigenesis. We examined the effect of AID deficiency on the generation of surface Ig-positive B cell lymphomas in Emu-cmyc transgenic mice. Almost all lymphomas that developed in AID-deficient transgenic mice were pre-B cell lymphomas, whereas control transgenic mice had predominantly B cell lymphomas, indicating that AID is required for development of B but not pre-B cell lymphomas from cmyc overexpressing tumor progenitors. Thus, AID may play multiple roles in B cell lymphomagenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AICDA (Activation-Induced Cytidine Deaminase)
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / enzymology
  • Cell Separation
  • Cytidine Deaminase / physiology*
  • DNA Damage
  • Gene Expression Regulation, Neoplastic*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • Mutation
  • Phenotype
  • Proto-Oncogene Proteins c-myc / metabolism
  • Proto-Oncogene Proteins c-pim-1 / genetics
  • Translocation, Genetic

Substances

  • Proto-Oncogene Proteins c-myc
  • Pim1 protein, mouse
  • Proto-Oncogene Proteins c-pim-1
  • AICDA (Activation-Induced Cytidine Deaminase)
  • Cytidine Deaminase