Altered Ig hypermutation pattern and frequency in complementary mouse models of DNA polymerase ζ activity

J Immunol. 2012 Jun 1;188(11):5528-37. doi: 10.4049/jimmunol.1102629. Epub 2012 Apr 30.


To test the hypothesis that DNA polymerase ζ participates in Ig hypermutation, we generated two mouse models of Pol ζ function: a B cell-specific conditional knockout and a knock-in strain with a Pol ζ mutagenesis-enhancing mutation. Pol ζ-deficient B cells had a reduction in mutation frequency at Ig loci in the spleen and in Peyer's patches, whereas knock-in mice with a mutagenic Pol ζ displayed a marked increase in mutation frequency in Peyer's patches, revealing a pattern that was similar to mutations in yeast strains with a homologous mutation in the gene encoding the catalytic subunit of Pol ζ. Combined, these data are best explained by a direct role for DNA polymerase ζ in Ig hypermutation.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • DNA-Directed DNA Polymerase / deficiency
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / physiology
  • Enzyme Activation / genetics
  • Enzyme Activation / immunology
  • Gene Knock-In Techniques
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Animal
  • Somatic Hypermutation, Immunoglobulin / genetics*
  • Somatic Hypermutation, Immunoglobulin / immunology*


  • DNA polymerase zeta
  • Rev3 protein, mouse
  • DNA-Directed DNA Polymerase