Polymerase mu is up-regulated during the T cell-dependent immune response and its deficiency alters developmental dynamics of spleen centroblasts

Eur J Immunol. 2005 May;35(5):1601-11. doi: 10.1002/eji.200526015.


Mammalian DNA polymerase mu (Polmu), preferentially expressed in secondary lymphoid organs, is shown here to be up-regulated in germinal centers after immunization. Alternative splicing appears to be part of Polmu regulation during an immune response. We generated Polmu-deficient mice that are viable and show no anatomical malformation or serious alteration in lymphoid populations, with the exception of an underrepresentation of the B cell compartment. Young and aged homozygous Polmu(-/-) mice generated similar immune responses after immunization with the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to chicken gammaglobulin (CGG), compared with their wild-type littermates. Nonetheless, the kinetics of development of the centroblast population showed significant differences. Hypermutation analysis of the rearranged heavy chain intron region in centroblasts isolated from NP-CGG-immunized Polmu(-/-) mice showed a similar quantitative and qualitative somatic mutation spectrum, but a lower representation of heavily mutated clones. These results suggest that although it is not a critical partner, Polmu modulates the in vivo somatic hypermutation process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Blotting, Southern
  • Blotting, Western
  • DNA-Directed DNA Polymerase / deficiency*
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / immunology*
  • Genetic Variation
  • In Situ Hybridization
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Reverse Transcriptase Polymerase Chain Reaction
  • Somatic Hypermutation, Immunoglobulin / immunology
  • Spleen / cytology*
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Up-Regulation


  • DNA polymerase mu
  • DNA-Directed DNA Polymerase