Switch recombination in normal IgA1+ B lymphocytes.
Switch recombination in normal IgA1+ B lymphocytes.
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正常 IgA1 B 淋巴细胞中的开关重组。
DOI：
10.1073/pnas.91.4.1323
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发表时间：
1994
影响因子：
11.1
通讯作者：
Radbruch,AH
中科院分区：
文献类型：
--
作者：
Irsch,J;Irlenbusch,S;Radl,J;Burrows,PD;Cooper,MD;Radbruch,AH
正常人大多数B淋巴细胞表达两类细胞表面免疫球蛋白：IgM和IgD。这两种抗原受体的特异性是相同的，因为它们是由相同的可变区基因片段转录和差异剪接到重链恒定区基因片段的mu和delta重链。B淋巴细胞表达其他免疫球蛋白同型，如IgG、IgA或IgE，是罕见的，而且没有很好的特征。尤其有争议的是它们的同型开关的分子机制。在这里，我们使用高梯度磁细胞分选和荧光活化细胞分选从人血液中纯化表面携带iga1的B淋巴细胞进行细胞和分子分析。这些细胞不表达除IgA1以外的任何免疫球蛋白类，并且在其他细胞表面分子的表达方面是一个相对统一的群体。在细胞周期和激活标记分析方面，它们是静止细胞。IgA1+细胞中类别转换的分子基础不是差异转录或剪接。相反，涉及DNA缺失的开关重组发生在两个免疫球蛋白重链基因位点上，包括等位基因排除的基因位点，并且在正常生理条件下似乎指向IgA1。
Most B lymphocytes in normal individuals express two classes of cell-surface immunoglobulins, IgM and IgD. The specificity of the two antigen receptors is identical since they are produced by transcription and differential splicing of the same variable region gene segment to the heavy-chain constant region gene segments for both mu and delta heavy chains. B lymphocytes expressing other immunoglobulin isotypes, IgG, IgA, or IgE, are rare and not well characterized. Particularly controversial is the molecular mechanism of their isotype switch. Here we use high-gradient magnetic cell sorting and fluorescence-activated cell sorting to purify surface IgA1-bearing B lymphocytes from human blood for cellular and molecular analysis. These cells express no immunoglobulin class other than IgA1 and are a relatively uniform population with regard to expression of other cell-surface molecules. They are resting cells in terms of cell cycle and activation marker analysis. The molecular basis for class switching in the IgA1+ cells is not differential transcription or splicing. Rather, switch recombination involving deletion of DNA has occurred on both immunoglobulin heavy-chain gene loci, including the allelically excluded one, and appears to have been directed to IgA1 under normal physiological conditions.