| 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. |
