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Chromosomal organization of the heavy chain variable region gene segments comprising the human fetal antibody repertoire.

机译:包含人类胎儿抗体库的重链可变区基因区段的染色体组织。

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摘要

The adult repertoire of antibody specificities is acquired in a developmentally programmed fashion that, in mouse and man, parallels the ordered rearrangement of a limited number of germ-line heavy chain variable region (VH) gene segments during development. It has been hypothesized that this developmental bias is a consequence of gene organization. In the mouse, rearrangement of VH gene segments proximal to the heavy chain joining region (JH) locus precedes rearrangement of genes located more distal to the JH locus. Similarly, in man, two VH elements located proximal to JH are expressed during fetal development. To test further this hypothesis in man, we have determined in a single individual the positions of an additional eight distinct VH elements known to comprise a significant fraction of the human developmental repertoire. These developmentally expressed VH elements were found to be dispersed over a region of 890 kilobases of the VH locus and were interspersed with other VH elements that are not known to be developmentally expressed. Thus, the ordered developmental expression of VH gene segments in man must involve mechanisms beyond physical proximity to the JH locus. Further, these results support the notion that fetal expression of VH gene segments is a regulated process and suggest that this regulation is important in the acquisition of immunocompetence.
机译:成年的抗体特异性库是通过以编程方式获得的,该方式在小鼠和人中与发育过程中有限数量的种系重链可变区(VH)基因区段的有序重排平行。据推测,这种发育偏差是基因组织的结果。在小鼠中,重链连接区(JH)基因座附近的VH基因片段的重排先于JH基因座更远的基因重排。类似地,在人类中,在胎儿发育过程中表达了位于JH附近的两个VH元素。为了进一步检验人的这一假说,我们已经在一个人中确定了另外八种不同的VH元素的位置,这些元素已知占人类发育谱的重要部分。发现这些发育表达的VH元件分散在VH基因座的890千碱基的区域上,并且散布在未知的尚未发育表达的其他VH元件中。因此,人体内VH基因片段的有序发育表达必须涉及与JH基因座物理接近的机制。此外,这些结果支持了VH基因区段的胎儿表达是受调节的过程的观点,并表明该调节在免疫能力的获得中很重要。

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