Yancopoulos George D, Alt Frederick W
Cell. 1985 Feb;40(2):271-81. doi: 10.1016/0092-8674(85)90141-2.
It is generally accepted that unrearranged immunoglobulin VH gene segments are not expressed and that assembly of a complete heavy chain gene is required to activate a previously silent VH promoter. We report that unrearranged VH gene segments are indeed expressed at a high level, but only in a developmentally controlled and tissue-specific manner. Unrearranged VH expression is limited to the very early stages of the B-lymphocyte differentiation pathway, and it is most prominent in cells undergoing VH to DJH rearrangement. Germ-line VH expression is independent of the heavy chain enhancer, may be controlled by 5' sequence elements, and is repressible by LPS. In contrast to earlier interpretations, our results demonstrate that the lack of unrearranged VH segment expression in mature, Ig-secreting cells is due to the inactivation of a previously active locus. These findings may provide insight into the mechanisms that control ordered rearrangement and allelic exclusion.
普遍认为未重排的免疫球蛋白VH基因片段不表达，并且完整重链基因的组装是激活先前沉默的VH启动子所必需的。我们报告未重排的VH基因片段确实以高水平表达，但仅以发育控制和组织特异性方式表达。未重排的VH表达仅限于B淋巴细胞分化途径的非常早期阶段，并且在经历VH到DJH重排的细胞中最为突出。种系VH表达独立于重链增强子，可能受5'序列元件控制，并且可被LPS抑制。与早期的解释相反，我们的结果表明，在成熟的Ig分泌细胞中缺乏未重排的VH片段表达是由于先前活跃的基因座失活。这些发现可能有助于深入了解控制有序重排和等位基因排斥的机制。
