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免疫球蛋白类别转换重组的调控

Control of immunoglobulin class switch recombination.

作者信息

Radbruch A, Burger C, Klein S, Müller W

出版信息

Immunol Rev. 1986 Feb;89:69-83. doi: 10.1111/j.1600-065x.1986.tb01473.x.

DOI:10.1111/j.1600-065x.1986.tb01473.x
PMID:3081434
Abstract

The comparative analysis of Ig class switch recombination in a priori IgG/IgA-expressing myelomas and hybridomas, in switch variants and in activated normal B cells shows the following characteristics of class switch recombination in activated B cells: It is prevented during most of B cell ontogeny. It happens on both IgH loci of activated and switched B cells. The recombination is programmed in that on both IgH loci of switched cells the same switch regions recombine with Smu. This is true at least for the IgG1 pathway. IgM-expressing cells show no class switch recombination on the inactive IgH locus. Thus, physiological class switch recombination is a programmed rather than a random event and is controlled as such. The initial stages of class switching and the molecules involved in these are largely unclear: What is the nature of the protection of switch regions and how is this protection abrogated? Do specific recombinases exist? What is the role of large transcription units? Is the specificity of class switch recombination a result of specific "opening" of the DNA for transcription? Do all B cells use the same switch mechanism? What is the role of switch factors (such as lymphokines)? These and more questions await answers and although a variety of switch scenarios could be discussed at present a detailed speculation seems premature.

摘要

对先验表达IgG/IgA的骨髓瘤细胞和杂交瘤细胞、转换变体以及活化的正常B细胞中Ig类别转换重组的比较分析显示了活化B细胞中类别转换重组的以下特征:在大多数B细胞个体发育过程中它受到抑制。它发生在活化和已转换B细胞的两个IgH基因座上。这种重组是程序性的,因为在已转换细胞的两个IgH基因座上,相同的转换区域与Smu重组。至少对于IgG1途径是这样。表达IgM的细胞在无活性的IgH基因座上不发生类别转换重组。因此,生理性类别转换重组是一个程序性而非随机事件,并受到相应的控制。类别转换的初始阶段以及其中涉及的分子在很大程度上尚不清楚:转换区域的保护性质是什么,以及这种保护是如何被消除的?是否存在特定的重组酶?大型转录单位的作用是什么?类别转换重组的特异性是DNA为转录而进行特定“开放”的结果吗?所有B细胞都使用相同的转换机制吗?转换因子(如淋巴因子)的作用是什么?这些以及更多问题有待解答,尽管目前可以讨论各种转换情况,但详细推测似乎为时过早。

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