Evidence for class-specific factors in immunoglobulin isotype switching.
Evidence for class-specific factors in immunoglobulin isotype switching.
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DOI：
10.1084/jem.191.8.1365
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发表时间：
2000-04-17
影响因子：
15.3
通讯作者：
Kenter, A L
中科院分区：
文献类型：
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作者：
Shanmugam, A;Shi, M J;Yauch, L;Stavnezer, J;Kenter, A L
免疫球蛋白类开关重组（SR）发生在B细胞特异性的染色体内开关区域之间的缺失过程。我们已经为SR开发了一种基于质粒的瞬时转染试验，以测试交易开关活性的存在。质粒是新颖的，因为它们缺乏DNA复制的真核起源。这些开关底物的重组活性仅限于支持内源性基因座的同型开关的B细胞系子集和有丝分裂原激活的正常脾B细胞。染色体外质粒重组所需的因子在增殖的脾B细胞和能够诱导对其染色体基因进行免疫球蛋白SR的B细胞系中组成性地表达。这些研究表明，诱导染色体开关的有丝分裂原诱导可接近性而不是开关重组酶活性。最后，我们提供了两种不同的开关活动的证据，它们独立地介导μ→α和μ→γ3 SR。
Immunoglobulin class switch recombination (SR) occurs by a B cell–specific, intrachromosomal deletional process between switch regions. We have developed a plasmid-based transient transfection assay for SR to test for the presence of transacting switch activities. The plasmids are novel in that they lack a eukaryotic origin of DNA replication. The recombination activity of these switch substrates is restricted to a subset of B cell lines that support isotype switching on their endogenous loci and to mitogen-activated normal splenic B cells. The factors required for extrachromosomal plasmid recombination are constitutively expressed in proliferating splenic B cells and in B cell lines capable of inducibly undergoing immunoglobulin SR on their chromosomal genes. These studies suggest that mitogens that induce switching on the chromosome induce accessibility rather than switch recombinase activity. Finally, we provide evidence for two distinct switching activities which independently mediate μ→α and μ→γ3 SR.