The transcription factor Spi-B is not required for somatic hypermutation.
The transcription factor Spi-B is not required for somatic hypermutation.
复制标题
体细胞超突变不需要转录因子 Spi-B。
DOI：
10.1016/s0161-5890(02)00201-8
复制
发表时间：
2003
影响因子：
3.6
通讯作者：
Storb,Ursula
中科院分区：
文献类型：
--
作者：
Kim,Nayun;Martin,TerenceE;Simon,MCeleste;Storb,Ursula
转录因子基因 Spi-B−/− 纯合失活的小鼠具有异常的 B 细胞功能和生发中心 (GC) 形成缺陷。我们在此报告，VH1 和 VH11 基因的体细胞超突变 (SHM) 在 Spi-B−/− 小鼠的派尔斑中并未减少。然而，突变模式显示可变区框架序列中替换突变与沉默突变的比率增加，这表明基于功能的突变 B 细胞的选择受到影响。为了支持这一点，来自 Spi-B 突变小鼠的六个序列中的两个在框架中具有点突变，这引入了与可变区中的另一个氨基酸的预测空间冲突。在 Spi-B 野生型小鼠生发中心 B 细胞的 120 个突变 VH1 或 VH11 基因中尚未观察到这种突变 (Leu81Phe)。该突变也不存在于同一 VH 家族的 136 个已发表的重链蛋白中。引起 Phe 变化的突变是 SHM 过程比颠换更青睐的转变。显然，Phe-81 必须相对频繁地出现，但在 Spi-B 野生型小鼠中并未被选择。
Mice with a homozygous inactivation of the transcription factor gene Spi-B−/−have abnormal B cell functions and a defect in germinal center (GC) formation. We report here that somatic hypermutation (SHM) of VH1 and VH11 genes is not diminished in Peyer’s patches of Spi-B−/−mice. However, the mutation pattern shows an increase in the ratio of replacement to silent mutations in the framework sequences of the variable regions, suggesting that selection of mutated B cells based on functionality is affected. In support of this, two of the six sequences from Spi-B mutant mice have a point mutation in the framework which introduces predicted steric clashes with another amino acid in the variable region. This mutation (Leu81Phe) has not been observed in 120 mutated VH1 or VH11 genes of germinal center B cells from Spi-B wildtype mice. The mutation also does not exist in any of 136 published heavy chain proteins of the same VH family. The mutations causing the change to Phe are transitions which are favored by the SHM process over transversions. Clearly, Phe-81 must arise relatively frequently, but is not selected in Spi-B wildtype mice.