Meyer K B, Teh Y M, Neuberger M S
Wellcome/CRC Institute of Developmental Biology and Cancer, Cambridge, UK.
Int Immunol. 1996 Oct;8(10):1561-8. doi: 10.1093/intimm/8.10.1561.
Ig kappa gene expression is controlled by two enhancers, one located within the major intron (Ei) and the other located downstream of C kappa (E3'). Whereas loss of E3' has previously been shown to diminish kappa expression, we show here that a rearranged kappa transgene lacking Ei is well expressed, even at the pre-B cell stage. This suggests that E3' alone might be sufficient to give properly regulated transcription throughout B cell development. Indeed, we show that a transgene composed of a beta-globin reporter linked to E3' is expressed in a B cell-specific manner, becoming activated at the late pro-B to pre-B cell stage but with dramatically enhanced activity on B cell activation. Thus, E3' becomes active as a transcription enhancer at the stage when V kappa-J kappa rearrangement is being initiated and is sufficient to yield an expression pattern in a linked reporter gene similar to that of fully rearranged kappa genes.
免疫球蛋白κ基因的表达受两个增强子控制,一个位于主要内含子内(Ei),另一个位于Cκ下游(E3')。虽然先前已表明E3'缺失会减少κ表达,但我们在此表明,一个缺少Ei的重排κ转基因即使在pre-B细胞阶段也能良好表达。这表明仅E3'可能足以在整个B细胞发育过程中实现适当调控的转录。事实上,我们表明,由与E3'相连的β-珠蛋白报告基因组成的转基因以B细胞特异性方式表达,在pro-B晚期到pre-B细胞阶段被激活,但在B细胞激活时活性显著增强。因此,E3'在Vκ-Jκ重排开始的阶段作为转录增强子变得活跃,并且足以在相连的报告基因中产生与完全重排的κ基因相似的表达模式。