Deletion of the Ig kappa light chain intronic enhancer/matrix attachment region impairs but does not abolish V kappa J kappa rearrangement
Deletion of the Ig kappa light chain intronic enhancer/matrix attachment region impairs but does not abolish V kappa J kappa rearrangement
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DOI：
10.1016/s1074-7613(00)80251-4
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发表时间：
1996-04-01
期刊：
影响因子：
32.4
通讯作者：
Baltimore, D
中科院分区：
文献类型：
--
作者：
Xu, Y;Davidson, L;Baltimore, D
在B细胞发育过程中，使用突变的胚胎干细胞（ES）细胞系（其中两条染色体上的整个区域被重组LoxP位点（E kappa ND）或PGK-新霉素抗性（PGK-neo（r））基因（E kappa NI）取代），研究了κ内含子增强子（iE kappa）及其相关基质附着区（MAR）的作用。来源于E kappa ND ES细胞的B细胞具有极大受损的V kappa J kappa重排，正常水平的kappa表达，并且kappa：lambda比率为1：1而不是通常的10：1。此外，从E kappa ND细胞衍生的产生Ekappa的杂交瘤显示很少的kappa重排。因此，MAR和iE kappa对于kappa重排具有定量意义，但不是必需的。此外，在E kappa NI ES细胞衍生的B细胞中可检测到很少的V kappa J kappa重排，证明插入的PGK-neo（r）基因显性抑制V kappa J kappa重排。
Roles of the kappa intronic enhancer (iE kappa) and its asssociated matrix attachment region (MAR) during B cell development were examined using mutant embryonic stem (ES) cell lines in which the entire region on both chromosomes was replaced with either a recombined LoxP site (E kappa ND) or the PGK-neomycin resistance (PGK-neo(r)) gene (E kappa NI). B cells derived from E kappa ND ES cells had greatly impaired V kappa J kappa rearrangement, normal levels of kappa expression, and kappa:lambda ratios of 1:1 instead of the usual 10:1. Furthermore, lambda-producing hybridomas derived from E kappa ND cells displayed little kappa rearrangement. Thus, the MAR and iE kappa are quantitatively significant for kappa rearrangement but not necessary. In addition, little V kappa J kappa rearrangement could be detected in B cells derived from E kappa NI ES cells, demonstrating that an inserted PGK-neo(r) gene dominantly suppresses V kappa J kappa rearrangement.