Lupus-specific antibodies reveal an altered pattern of somatic mutation
Lupus-specific antibodies reveal an altered pattern of somatic mutation
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DOI：
10.1172/jci119796
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发表时间：
1997-11-15
影响因子：
15.9
通讯作者：
Diamond, B
中科院分区：
文献类型：
--
作者：
ManheimerLory, AJ;ZandmanGoddard, G;Diamond, B
F4独特型是一种几乎仅在IgG免疫球蛋白上表达的重链决定簇，并且与双链DNA的特异性高度相关。由于高滴度F4表达主要存在于系统性红斑狼疮（SLE）患者的血清中，我们认为F4（+）IgG抗体可能构成一个有用的免疫球蛋白亚群，用于研究可变（V）的狼疮特异性改变，对狼疮患者产生的F4（+）B细胞系的分子分析表明，尽管F4反应性与对天然DNA的特异性强相关，但没有明显的VH基因限制。此外，编码这些抗体的VH基因片段也用于保护性免疫应答。对F4（+）抗体中体细胞突变过程的检查显示，体细胞突变频率以及互补决定区或框架区的突变分布均无异常，但是，突变对推定突变热点的靶向减少，这些抗体中存在的突变的这种细微差异可能反映了突变机制的内在缺陷，或者更可能是影响突变过程的B细胞活化状态的改变，也可能是负选择。
The F4 idiotype is a heavy chain determinant expressed almost exclusively on IgG immunoglobulins and is highly associated with specificity for double-stranded DNA, Since high-titered F4 expression is present predominantly in sera of patients with systemic lupus erythematosus (SLE), we thought F4(+) IgG antibodies might constitute a useful subset of immunoglobulins in which to investigate lupus-specific alterations in variable (V) region gene expression or in the process of somatic mutation, This molecular analysis of F4(+) B cell lines generated from lupus patients demonstrates that despite the strong association of F4 reactivity with specificity for native DNA, there is no apparent VH gene restriction. Furthermore, VH gene segments encoding these antibodies are also used in protective immune responses.An examination of the process of somatic mutation in F4(+) antibodies showed no abnormality in frequency of somatic mutation nor in the distribution of mutations in complementarity-determining regions or framework regions, However, there was a decrease in targeting of mutations to putative mutational hot spots, This subtle difference in mutations present in these antibodies may reflect an intrinsic defect in mutational machinery or, more likely, altered state of B cell activation that affects the mutational process and perhaps also negative selection.