CIRCULAR DNA IS A PRODUCT OF THE IMMUNOGLOBULIN CLASS SWITCH REARRANGEMENT
CIRCULAR DNA IS A PRODUCT OF THE IMMUNOGLOBULIN CLASS SWITCH REARRANGEMENT
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DOI：
10.1038/345452a0
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发表时间：
1990-05-31
期刊：
影响因子：
64.8
通讯作者：
WABL, M
中科院分区：
文献类型：
--
作者：
VONSCHWEDLER, U;JACK, HM;WABL, M
免疫球蛋白的类别是由其重链的恒定区定义的。当B淋巴细胞转换其产生的重链类型时，µ型重链的恒定区被替换（参见参考文献1和2，参见参考文献3）;这通过DNA重排发生，使编码新恒定区的基因片段靠近编码可变区的VDJ片段。前B细胞系18-81在培养过程中从产生重链µ转换为产生γ2b 4，5，偶尔会异常重排重链基因座，从而使µ和γ2b转换区域之间的DNA序列发生反转6。因为环出是生成反转的中间步骤，所以开关重排可以通过环出和删除来发生。如果重组是相互的，这将产生一个DNA环。事实上，环状DNA分子已被分离为编码T细胞受体可变区7，9和免疫球蛋白重链可变区10，11和轻链可变区11，12的基因片段之间重排的产物。但是，尽管可变区重排的断点被精确定义，但任何给定重链类别转换的断点分散在>6个碱基的长度上，包括两个转换区。我们现在已经分离出含有通过类别转换缺失的序列的环状DNA，从而表明免疫球蛋白重链类别转换通过环出和缺失发生。
THE class of immunoglobulin is defined by the constant region of its heavy chain. When a B lymphocyte switches the class of heavy chain it produces, the constant region ofµ-type heavy chain is replaced (reviewed in refs 1 and 2, and see ref. 3); this occurs through a DNA rearrangement that brings the gene segment encoding the new constant region close to theVDJsegment encoding the variable region. The pre-B-cell line 18-81, which switches from heavy chainµtoγ2b production in culture4,5, occasionally abnormally rearranges the heavy chain locus so that DNA sequences between the switch regions ofµandγ2b are inverted6. Because looping-out is an intermediate step in generating an inversion, the switch rearrangement could occur by looping-out and deletion. Provided that recombination is reciprocal, this would produce a circle of DNA. Indeed, circular DNA molecules have been isolated as products of rearrangement among gene segments encoding the variable regions of the T-cell receptor7,9and of the immunoglobulin heavy chain10,11and light chain11,12. But whereas the breakpoints for the variable region rearrangement are precisely defined, the breakpoints for any given heavy chain class switch are scattered over a length of >6 kilobases, including both switch regions. We have now isolated circular DNA containing the sequences deleted by class-switching, thereby showing that the immunoglobulin heavy chain class switch occurs through looping-out and deletion.