Polymerase mu is up-regulated during the T cell-dependent immune response and its deficiency alters developmental dynamics of spleen centroblasts.
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.
Lucas
Daniel
D
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
Laín de Lera
Teresa
T
González
Manuel A
MA
Ruiz
Jose F
JF
Domínguez
Orlando
O
Casanova
Jesús C
JC
Martínez-A
Carlos
C
Blanco
Luis
L
Bernad
Antonio
A
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
C407743:DNA polymerase mu; D004259:DNA-Directed DNA Polymerase