The early expression of some human autoantibody-associated heavy chain variable region genes is controlled by specific regulatory elements.
The early expression of some human autoantibody-associated heavy chain variable region genes is controlled by specific regulatory elements.
复制标题
一些人类自身抗体相关重链可变区基因的早期表达受到特定调控元件的控制。
DOI：
10.1111/j.1365-3083.1990.tb02818.x
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发表时间：
1990
影响因子：
3.7
通讯作者：
Carson,DA
中科院分区：
文献类型：
--
作者：
Chen,PP;Soto-Gil,RW;Carson,DA
最近的分子克隆研究表明，一些自身抗体可能由种系 Ig 可变 (V) 基因直接编码，而没有任何体细胞突变，这强烈表明此类自身抗体具有重要的生理学意义。对人胎儿肝脏中 Ig 基因表达的独立分析表明，在 100-200 个潜在种系 Vh 基因库中，仅使用了 9 个重链 V (Vh) 基因。我们观察到这九个Vh基因中有四个编码与人类自身抗体重链相同或几乎相同的序列。这种意想不到的重叠意味着一些自身抗体在早期发育过程中优先表达。最近对胎儿肝脏中表达的两个 Vh3 基因的结构分析显示，fianking 区域中的增强子样序列比典型 Vh 基因预期的要多得多。据推测，这些自身抗体相关的 Vh 基因可能包含各种顺式调节元件的组合，这些组合影响了它们在早期个体发育过程中的特异性表达。此外，这些观察结果与网络假设一致，该假设表明早期 B 细胞发育是由自我反应驱动的。自身抗体基因中的顺式调节元件可能与已被证明促进 Vh 基因接合的位置效应协同作用。
Recent molecular cloning studies have revealed that some autoantibodies may be encoded directly by germline Ig variable (V) genes without any somatic mutation, suggesting strongly that such autoantibodies are physiologically important. Independent analyses of Ig gene expression in a human fetal liver showed that only nine heavy chain V (Vh) genes were used, out of a potential germline Vh gene repertoire of 100–200. We have observed that four of these nine Vh genes encode sequences identical or almost identical to human autoantibody heavy chains. This unexpected overlap implies that some autoantibodies are expressed preferentially during early development. Recent structural analyses of two Vh3 genes expressed in fetal liver revealed many more enhancer‐like sequences in the fianking regions than expected for a typical Vh gene. It is hypothesized that these autoantibody‐related Vh genes may contain various combinations ofcisregulatory elements which infiuence their specific expression during early ontogenic development. Furthermore, these observations are consistent with network hypotheses, which suggest that early B‐cell development is driven by reactivity with self. Thecisregulatory elements in the autoantibody genes may act in concert with the positional effects that have been shown to facilitate Vh gene engagement.