title: 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.
abstract: 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.
authors.affiliation: Institute for Genetics, University of Cologne, D-50931 Cologne, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Esposito
authors.forename: G
authors.initials: G
authors.lastname: Texido
authors.forename: U A
authors.initials: UA
authors.lastname: Betz
authors.forename: H
authors.initials: H
authors.lastname: Gu
authors.forename: W
authors.initials: W
authors.lastname: Müller
authors.forename: U
authors.initials: U
authors.lastname: Klein
authors.forename: K
authors.initials: K
authors.lastname: Rajewsky
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D019951:DNA Polymerase beta / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D004260:DNA Repair; D016332:Fetal Tissue Transplantation; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D005804:Genes, Lethal; D018858:Germinal Center / Q000166:cytology; D007111:Immunity, Cellular; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D016031:Liver Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D009030:Mosaicism; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000276:immunology*; D045567:VDJ Recombinases
chemical_list: D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases; D019951:DNA Polymerase beta