Role for mismatch repair proteins Msh2, Mlh1, and Pms2 in immunoglobulin class switching shown by sequence analysis of recombination junctions.
Role for mismatch repair proteins Msh2, Mlh1, and Pms2 in immunoglobulin class switching shown by sequence analysis of recombination junctions.
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DOI：
10.1084/jem.20011877
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发表时间：
2002-02-04
期刊：
影响因子：
--
通讯作者：
Stavnezer J
中科院分区：
文献类型：
--
作者：
Schrader CE;Vardo J;Stavnezer J
来自错配修复（MMR）蛋白缺陷的小鼠的B细胞在体外和体内表现出经历类别转换重组的能力降低。在体外培养的B细胞中，这种缺陷不伴随细胞活力的任何降低或细胞周期的改变。为了评估MMR在转换中的作用，我们检测了培养中诱导脾B细胞转换为IgG 3的Sμ-Sγ3重组连接的核苷酸序列。数据表明，与Msh 2-、Mlh 1-和Pms 2-缺陷型B细胞相比，野生型B细胞中开关连接的序列存在明显差异。Msh 2缺陷细胞的开关接头序列显示，相对于野生型细胞的接头，Sμ和Sγ3之间的微同源性长度减少，插入增加，即，这些核苷酸似乎不来源于Sμ或Sγ3亲本序列。相比之下，23%的路口Mlh 1和Pms 2缺陷细胞发生在异常长的延伸微同源。这些数据表明，MMR蛋白直接参与类转换，Msh 2的作用不同于Mlh 1和Pms 2。
B cells from mice deficient in mismatch repair (MMR) proteins show decreased ability to undergo class switch recombination in vitro and in vivo. The deficit is not accompanied by any reduction in cell viability or alterations in the cell cycle in B cells cultured in vitro. To assess the role of MMR in switching we examined the nucleotide sequences of Sμ-Sγ3 recombination junctions in splenic B cells induced in culture to switch to IgG3. The data demonstrate clear differences in the sequences of switch junctions in wild-type B cells in comparison with Msh2-, Mlh1-, and Pms2-deficient B cells. Sequences of switch junctions from Msh2-deficient cells showed decreased lengths of microhomology between Sμ and Sγ3 relative to junctions from wild-type cells and an increase in insertions, i.e., nucleotides which do not appear to be derived from either the Sμ or Sγ3 parental sequence. By contrast, 23% of junctions from Mlh1- and Pms2-deficient cells occurred at unusually long stretches of microhomology. The data indicate that MMR proteins are directly involved in class switching and that the role of Msh2 differs from that of Mlh1 and Pms2.
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