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

Abstract

Mammalian DNA polymerase μ (Polμ), 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 Polμ regulation during an immune response. We generated Polμ-deficient mice that are viable and show no anatomical malformation or serious alteration in lymphoid populations, with the exception of an under-representation of the B cell compartment. Young and aged homozygous Polμ-/- 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 Polμ-/- 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, Polμ modulates the in vivo somatic hypermutation process. © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.