Arulampalam V, Grant P A, Samuelsson A, Lendahl U, Pettersson S
Center for Biotechnology, Novum, Karolinska Institute, Stockholm, Huddinge, Sweden.
Eur J Immunol. 1994 Jul;24(7):1671-7. doi: 10.1002/eji.1830240732.
To execute different biological functions, the expression pattern of immunoglobulin heavy chain genes (IgH) is altered during B lymphocyte differentiation. Early in B cell differentiation, it is assumed that the heavy chain promoter and the intragenic enhancer (E mu) ensure VDJ recombination. This leads to the expression of the immunoglobulin receptor on the cell surface. An additional strong enhancer in the far 3' end of the IgH locus has, however, prompted a re-evaluation of the regulation of immunoglobulin gene expression. To define the temporal and spatial regulation of the IgH 3' enhancer, transgenic mice harboring an enhancer-dependent reporter gene construct were generated. Here we demonstrate that IgH 3' enhancer activity is largely restricted to activated immunocompetent B cells. Furthermore, the enhancer can be transactivated following mitogen stimulation with lipopolysaccharide and 12-O-tetradecanoylphorbol 13-acetate. We propose a model whereby 3' enhancer activation is linked to the activation of resting immunocompetent B cells. The implications of the enhancer being active in late B lymphocyte differentiation, when heavy chain class switching occurs, are discussed.
为了执行不同的生物学功能，免疫球蛋白重链基因（IgH）的表达模式在B淋巴细胞分化过程中会发生改变。在B细胞分化早期，人们认为重链启动子和基因内增强子（Eμ）可确保VDJ重组。这导致免疫球蛋白受体在细胞表面表达。然而，IgH基因座远3'端的另一个强增强子促使人们对免疫球蛋白基因表达的调控进行重新评估。为了确定IgH 3'增强子的时空调控，构建了携带依赖增强子的报告基因构建体的转基因小鼠。在此我们证明，IgH 3'增强子活性主要局限于活化的免疫活性B细胞。此外，在用脂多糖和12-O-十四酰佛波醇-13-乙酸酯进行有丝分裂原刺激后，该增强子可被反式激活。我们提出了一个模型，即3'增强子激活与静止免疫活性B细胞的激活相关。文中讨论了该增强子在重链类别转换发生的晚期B淋巴细胞分化中具有活性的意义。
