Pettersson S, Cook G P, Brüggemann M, Williams G T, Neuberger M S
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Nature. 1990 Mar 8;344(6262):165-8. doi: 10.1038/344165a0.
The expression of immunoglobulin heavy-chain (IgH) genes is generally thought to be regulated by the combination of the VH promoter with the enhancer element which is located in the JH-CH intron. This is probably an oversimplification: there are cell lines that transcribe IgH genes despite the deletion of the intron-enhancer. These findings could imply that other enhancer element(s) exist in the IgH locus. Here we show that a strong B-cell-specific enhancer is indeed located at the 3'-end of the rat IgH locus, 25 kilobases downstream of C alpha. This enhancer should be retained downstream of all rearranged IgH genes, regardless of the VH or CH segment used. Taken together with analogous findings for the mouse kappa locus, the results prompt a re-evaluation of the mechanism of regulation of immunoglobulin gene transcription. Furthermore, unlike the intron-enhancer, the IgH 3' enhancer would become linked to a c-myc that rearranges into an IgH switch region. The IgH 3' enhancer could therefore play a part in the activation of the translocated c-myc genes in rat immunocytomas, mouse plasmacytomas and Burkitt lymphomas.
免疫球蛋白重链（IgH）基因的表达通常被认为是由VH启动子与位于JH-CH内含子中的增强子元件共同调控的。这可能过于简单化了：有些细胞系尽管缺失了内含子增强子，仍能转录IgH基因。这些发现可能意味着IgH基因座中存在其他增强子元件。我们在此表明，一个强大的B细胞特异性增强子确实位于大鼠IgH基因座的3'端，在Cα下游25千碱基处。无论使用何种VH或CH片段，该增强子都应保留在所有重排的IgH基因下游。结合小鼠κ基因座的类似发现，这些结果促使人们重新评估免疫球蛋白基因转录的调控机制。此外，与内含子增强子不同，IgH 3'增强子会与重排到IgH转换区的c-myc相连。因此，IgH 3'增强子可能在大鼠免疫细胞瘤、小鼠浆细胞瘤和伯基特淋巴瘤中易位的c-myc基因的激活中发挥作用。
