title: Polymerase mu is up-regulated during the T cell-dependent immune response and its deficiency alters developmental dynamics of spleen centroblasts.
abstract: 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.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lucas
authors.forename: Teresa
authors.initials: T
authors.lastname: Laín de Lera
authors.forename: Manuel A
authors.initials: MA
authors.lastname: González
authors.forename: Jose F
authors.initials: JF
authors.lastname: Ruiz
authors.forename: Orlando
authors.initials: O
authors.lastname: Domínguez
authors.forename: Jesús C
authors.initials: JC
authors.lastname: Casanova
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
authors.forename: Luis
authors.initials: L
authors.lastname: Blanco
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernad
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D014644:Genetic Variation; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
chemical_list: C407743:DNA polymerase mu; D004259:DNA-Directed DNA Polymerase