Mice reconstituted with DNA polymerase beta-deficient fetal liver cells are able to mount a T cell-dependent immune response and mutate their Ig genes normally

Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1166-71. doi: 10.1073/pnas.97.3.1166.


The ubiquitously expressed, error-prone DNA polymerase beta (polbeta) plays a role in base excision repair, and the involvement of this molecule in the nonhomologous end joining (NHEJ) process of DNA repair has recently been demonstrated in yeast. Polbeta-deficient mice are not viable, and studies on conditional mutants revealed a competitive disadvantage of polbeta(-/-) vs. wild-type cells. We show here that polbeta-deficient mice survive up to day 18.5 postcoitum, but die perinatally; a circumstance that allowed the investigation of a potential role of polbeta in lymphocyte development by transfer of fetal liver cells (FLC) derived from polbeta(-/-) embryos into lethally irradiated hosts. FLC transfers using mutant cells lead to an almost normal reconstitution of the lymphocyte compartment, indicating that polbeta-deficiency does not prevent V(D)J recombination, which is known to employ factors of the NHEJ pathway. Mice reconstituted with polbeta(-/-) FLC mount a normal T cell-dependent immune response against the hapten (4-hydroxy-3-nitrophenyl) acetyl (NP). Moreover, germinal center B cells from NP-immunized reconstituted mice show normal levels and patterns of somatic point mutations in their rearranged antibody genes, demonstrating that polbeta is not critically involved in somatic hypermutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • DNA Nucleotidyltransferases / metabolism
  • DNA Polymerase beta / deficiency*
  • DNA Polymerase beta / genetics
  • DNA Polymerase beta / physiology
  • DNA Repair
  • Fetal Tissue Transplantation*
  • Gene Rearrangement, B-Lymphocyte*
  • Genes, Immunoglobulin*
  • Genes, Lethal
  • Germinal Center / cytology
  • Immunity, Cellular
  • Liver / embryology
  • Liver / enzymology*
  • Liver Transplantation*
  • Mice
  • Mice, Inbred C57BL
  • Mosaicism
  • Radiation Chimera
  • T-Lymphocytes / immunology*
  • VDJ Recombinases


  • DNA Nucleotidyltransferases
  • VDJ Recombinases
  • DNA Polymerase beta