Decreased Frequency of Somatic Hypermutation and Impaired Affinity Maturation but Intact Germinal Center Formation in Mice Expressing Antisense RNA to DNA Polymerase ζ

摘要: To examine a role of DNA polymerase zeta in somatic hypermutation, we generated transgenic mice that express antisense RNA to portion mouse REV3, the gene encoding this polymerase. These high levels RNA, significantly reducing endogenous REV3 transcript. Following immunization hapten-protein complex, mounted vigorous Ab responses, accomplished switch IgG, and formed numerous germinal centers. However, most animals, generation affinity Abs was delayed. In addition, accumulation mutations V(H) genes memory B cells from decreased, particularly among those generate amino acid replacements enhance cell receptor hapten. data implicate zeta, nonreplicative polymerase, process maturation, possibly through clonal selection, or both.