Identification of Transcriptional Factor(s) which regulates Ig gene expression

免疫球蛋白重链（IgH）基因的表达在很大程度上受IgH基因内含子增强子的调控，该增强子由某些蛋白结合基序组成。这些基序作为DNA元件，对IgH基因转录的调节是重要的。这些基序中的两个，人IgH基因内含子增强子中的HE2和E6，被认为影响B细胞特异性基因表达。发现E6在非淋巴细胞中起沉默者的作用。因此，研究这些元件的调控分子及其在体内的功能具有重要意义。为了检测HE2和E6基序在体内的真实功能，我们建立了转基因小鼠系。含有活性HE2基序的IgH基因内含子增强子3 ′端缺失突变体具有与完整IgH基因内含子增强子相同的转录活性和组织特异性。此外，通过酶联免疫吸附试验，在细胞水平上证实了HE2基序在IgH基因内含子增强子的组织特异性活性中起重要作用。在转基因小鼠中，IgH基因内含子增强子不仅在B淋巴细胞中起作用，而且在类似于神经胶质细胞的脉络丛细胞中也起作用。这表明免疫系统和神经系统之间存在共同的基因表达控制机制。

Immunoglobulin heavy-chain (IgH) gene expression is regulated in a large part by the IgH gene intronic enhancer which is composed of certain protein-binding motifs. These motifs act as a DNA element which is important for the regulation of the IgH gene trasncription. Two of these motifs, HE2 and E6 in the human IgH gene intronic enhancer, are considered to affect the B cell-specific gene expression. E6 was found to function as a silencer in non-lymphoid cells. It is very important to identify the regulatory molecules acting on these elements and their in vivo function. To examine the true function of the HE2 and E6 motifs in vivo, we established transgenic mouse lines. A 3^'deletion mutant of the IgH gene intronic enhancer which includes an active HE2 motif showed almost the same degree of trnascriptional activity and tissue-specificity as the whole IgH gene intronic enhancer. Still more, using the luciferase-assay, it was confirmed at cellular level that the HE2 motif plays an important role in the tissue-specific activity of the IgH gene intronic enhancer. On the other hand, the E6 motif was in some non-B cells.In transgenic mice, the IgH gene intronic enhancer functioned not only in B-lymphocytes but also in choroid plexus cells which are similar to glial cells. This suggests the existence of common gene expression control mechanisms between the immune system and the nervous system.