Qualitative changes in the subunit composition of kappa B-binding complexes during murine B-cell differentiation.

We report here that the major kappa B-binding complex in murine mature B cells is composed of a p50-Rel heterodimer, whereas the major inducible form in pre-B cells is a p50-p65 heterodimer. Treatment of a pre-B-cell line with lipopolysaccharide changes the subunit composition of kappa B-binding complexes from p50-p65 to p50-Rel. This change is preceded by the enhanced Rel expression and correlates with the expression of the gene for the immunoglobin kappa light chain. The heterodimeric p50-Rel complex binds to the intronic enhancer-kappa B site in the immunoglobulin kappa light chain gene at least 20-fold more stably than does the p50-p65 dimer. These data support a model in which augmentation of Rel expression during the differentiation of pre-B cells to mature B cells leads to an exchange of kappa B-binding subunits resulting in the transcriptional activation of the gene for the immunoglobulin kappa light chain. IMAGES:

本研究报道，小鼠成熟B细胞中的主要κB结合复合物（kappa B-binding complex）由p50-Rel异二聚体构成，而前B细胞中的主要诱导型κB结合复合物则为p50-p65异二聚体。采用脂多糖（lipopolysaccharide）处理前B细胞系后，其κB结合复合物的亚基组成会从p50-p65转变为p50-Rel。这一亚基替换过程发生于Rel表达上调之后，且与免疫球蛋白κ轻链（immunoglobulin kappa light chain）基因的表达水平密切相关。异二聚体p50-Rel复合物与免疫球蛋白κ轻链基因内含子增强子-κB位点（intronic enhancer-kappa B site）的结合稳定性，至少比p50-p65二聚体高20倍。上述数据支持如下模型：在前B细胞向成熟B细胞分化的过程中，Rel表达的上调会引发κB结合亚基的替换，最终导致免疫球蛋白κ轻链基因的转录激活。IMAGES: