Kim Nayun, Martin Terence E, Simon M Celeste, Storb Ursula
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Mol Immunol. 2003 Jan;39(10):577-83. doi: 10.1016/s0161-5890(02)00201-8.
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.
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，Spi-B(-)/(-)小鼠的派尔集合淋巴结中VH1和VH11基因的体细胞高频突变（SHM）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例增加，这表明基于功能对突变B细胞的选择受到影响。支持这一点的是，来自Spi-B突变小鼠的六个序列中有两个在框架中有一个点突变，该突变与可变区中的另一个氨基酸产生预测的空间冲突。这种突变（Leu81Phe）在Spi-B野生型小鼠生发中心B细胞的120个突变VH1或VH11基因中未观察到。该突变在同一VH家族已发表的136种重链蛋白中也不存在。导致变为苯丙氨酸的突变是转换，在SHM过程中转换比颠换更受青睐。显然，苯丙氨酸-81肯定相对频繁地出现，但在Spi-B野生型小鼠中未被选择。
