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Publication : DNA polymerase eta is a limiting factor for A:T mutations in Ig genes and contributes to antibody affinity maturation.

First Author  Masuda K Year  2008
Journal  Eur J Immunol Volume  38
Issue  10 Pages  2796-805
PubMed ID  18825746 Mgi Jnum  J:143471
Mgi Id  MGI:3826960 Doi  10.1002/eji.200838502
Citation  Masuda K, et al. (2008) DNA polymerase eta is a limiting factor for A:T mutations in Ig genes and contributes to antibody affinity maturation. Eur J Immunol 38(10):2796-805
abstractText  DNA polymerase eta (POLH) is required for the generation of A:T mutations during the somatic hypermutation of Ig genes in germinal center B cells. It remains unclear, however, whether POLH is a limiting factor for A:T mutations and how the absence of POLH might affect antibody affinity maturation. We found that the heterozygous Polh+/- mice exhibited a significant reduction in the frequency of A:T mutations in Ig genes, with each type of base substitutions at a level intermediate between the Polh+/+ and Polh(-/-) mice. These observations suggest that Polh is haplo-insufficient for the induction of A:T mutations in Ig genes. Intriguingly, there was also a reduction of C to T and G to A transitions in Polh+/- mice as compared with WT mice. Polh(-/-) mice produced decreased serum titers of high-affinity antibodies against a T-dependent antigen, which was associated with a significant reduction in the number of plasma cells secreting high-affinity antibodies. Analysis of the V region revealed that aa substitutions caused by A:T mutations were greatly reduced in Polh(-/-) mice. These results demonstrate that POLH is a limiting factor for A:T mutations and contributes to the efficient diversification of Ig genes and affinity maturation of antibodies.
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