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

First Author  Lucas D Year  2005
Journal  Eur J Immunol Volume  35
Issue  5 Pages  1601-11
PubMed ID  15789338 Mgi Jnum  J:97782
Mgi Id  MGI:3576407 Doi  10.1002/eji.200526015
Citation  Lucas D, et al. (2005) Polymerase mu is up-regulated during the T cell-dependent immune response and its deficiency alters developmental dynamics of spleen centroblasts. Eur J Immunol 35(5):1601-11
abstractText  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.
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