ALLELIC EXCLUSION IN TRANSGENIC MICE THAT EXPRESS THE MEMBRANE FORM OF IMMUNOGLOBULIN-MU
ALLELIC EXCLUSION IN TRANSGENIC MICE THAT EXPRESS THE MEMBRANE FORM OF IMMUNOGLOBULIN-MU
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DOI：
10.1126/science.3107126
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发表时间：
1987-05-15
期刊：
影响因子：
56.9
通讯作者：
LEDER, P
中科院分区：
文献类型：
--
作者：
NUSSENZWEIG, MC;SHAW, AC;LEDER, P
产生抗体的细胞表现出一种特殊的调节形式，即每个细胞仅从其两组抗体基因中的一组产生免疫球蛋白。这种现象被称为等位基因排斥，被认为是由一个重链等位基因限制另一个重链等位基因表达的产物介导的。重链以分泌型和膜结合型两种分子形式合成。为了确定是否是免疫球蛋白M （IgM）重链（.mu）的膜结合形式特异性地介导了这种调节，创建了携带人类.mu的转基因小鼠。链基因的改变使得它只能指导膜结合蛋白的合成。人类细胞的膜结合形式。通过信使RNA和表面免疫球蛋白的测定，这些动物的大多数B细胞都产生了这种链。此外，许多表达人基因的B细胞不表达内源性小鼠IgM，少数表达内源性小鼠.mu的B细胞。不表达转基因。因此，.mu的膜结合形式。这条链足以介导等位基因排斥。此外，用于此目的的分子结构在人类和小鼠系统之间是保守的。
Antibody-producing cells display a special form of regulation whereby each cell produces immunoglobulin from only one of its two sets of antibody genes. This phenomenon, called allelic exclusion, is thought to be mediated by the product of one heavy chain allele restricting the expression of the other. Heavy chains are synthesized in two molecular forms, secreted and membrane bound. In order to determine whether it is specifically the membrane-bound form of the immunoglobulin M (IgM) heavy chain (.mu.) that mediates this regulation, transgenic mice were created that carry a human .mu. chain gene altered so that it can only direct the synthesis of the membrane-bound protein. The membrane-bound form of the human .mu. chain was made by most of the B cells in these animals as measured by assays of messenger RNA and surface immunoglobulins. Further, the many B cells that express the human gene do not express endogenous mouse IgM, and the few B cells that express endogenous mouse .mu. do not express the transgene. Thus, the membrane-bound form of the .mu. chain is sufficient to mediate allelic exclusion. In addition, the molecular structures recognized for this purpose are conserved between human and mouse systems.