Protein Interactions in Antibody Diversity

基于Polq-/-小鼠突变频率和谱的改变的几个报道，DNA聚合酶theta已被牵连在免疫球蛋白可变基因的体细胞超突变过程中。 然而，这些研究在突变频率和核苷酸取代类型上有着截然不同的结果，这对聚合酶theta在超突变中的作用提出了质疑。 DNA聚合酶eta对突变具有显性作用，并且在聚合酶theta不存在的情况下可以替代以影响模式。 因此，我们研究了聚合酶eta和theta缺陷小鼠的突变。 Peyers集合淋巴结重排可变基因的突变频率在野生型、Polq-/-、Polh-/-和Polq-/-Polh-/-小鼠中相似。 在野生型和Polq-/-克隆之间，以及在Polh-/-和Polq-/-Polh-/-克隆之间，置换的类型也相似。 此外，四组小鼠脾B细胞中的重链类别转换无差异。 这些结果表明，聚合酶θ在免疫球蛋白基因体细胞突变的产生中不起重要作用。

DNA polymerase theta has been implicated in the process of somatic hypermutation in immunoglobulin variable genes based on several reports of alterations in the frequency and spectra of mutations from Polq-/- mice. However, these studies have contrasting results on mutation frequencies and the types of nucleotide substitutions, which question the role of polymerase theta in hypermutation. DNA polymerase eta has a dominant effect on mutation and may substitute in the absence of polymerase theta to affect the pattern. Therefore, we have examined mutation in mice deficient for both polymerases eta and theta. The mutation frequencies in rearranged variable genes from Peyers patches were similar in wild type, Polq-/-, Polh-/-, and Polq-/-Polh-/- mice. The types of substitutions were also similar between wild type and Polq-/- clones, and between Polh-/- and Polq-/-Polh-/- clones. Furthermore, there was no difference in heavy chain class switching in splenic B cells from the four groups of mice. These results indicate that polymerase theta does not play a significant role in the generation of somatic mutation in immunoglobulin genes.