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

Keiji Masuda, Rika Ouchida, Masayuki Yokoi, Fumio Hanaoka, Takachika Azuma, Ji Yang Wang

研究成果: ジャーナルへの寄稿学術誌査読

14 被引用数 (Scopus)

抄録

DNA polymerase η (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/- 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 mice. 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.

本文言語英語
ページ(範囲)2796-2805
ページ数10
ジャーナルEuropean Journal of Immunology
38
10
DOI
出版ステータス出版済み - 12月 1 2008
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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