Grumont R J, Gerondakis S
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Cell Growth Differ. 1994 Dec;5(12):1321-31.
The transcription factor NF-kappa B, shown to be essential for expression of the immunoglobulin C kappa gene, is a key regulatory component in pre-B to B-cell differentiation. While previous studies have used lymphoid cell line models, here we examine the expression and subunit composition of rel/NF-kappa B complexes in normal murine pre-B and B lymphocytes. Two major NF-kappa B complexes are detected in pre-B and B cells. A high mobility complex, found in pre-B (Cb) and B cells (C beta) is a homodimer of the NF-kappa B subunit p50. In pre-B cells, the slower migrating complex (Ca), which is predominantly cytoplasmic, is largely comprised of p50 and p65, whereas in B cells, a nuclear and cytoplasmic complex (C alpha) of identical mobility to Ca mainly consists of p50 and p75c-rel. While p50 and p65 levels do not change during pre-B to B-cell differentiation, p75c-rel is 5- to 6-fold more abundant in B cells compared to pre-B cells, a finding consistent with the switch in NF-kappa B subunit usage. During lipopolysaccharide-induced B-cell proliferation, transient up-regulation of both the nuclear p50 homodimer and p75c-rel containing complex is mirrored by a concurrent increase in c-rel and p105 but not p65 mRNA expression, a finding consistent with rel-NF-kappa B expression in B cells being controlled by an autoregulatory mechanism.
转录因子NF-κB对免疫球蛋白Cκ基因的表达至关重要,是前B细胞向B细胞分化过程中的关键调节成分。虽然先前的研究使用了淋巴细胞系模型,但在此我们研究正常小鼠前B淋巴细胞和B淋巴细胞中rel/NF-κB复合物的表达及亚基组成。在前B细胞和B细胞中检测到两种主要的NF-κB复合物。在前B细胞(Cb)和B细胞(Cβ)中发现的一种高迁移率复合物是NF-κB亚基p50的同二聚体。在前B细胞中,迁移较慢的复合物(Ca)主要位于细胞质中,主要由p50和p65组成,而在B细胞中,与Ca迁移率相同的一种核质复合物(Cα)主要由p50和p75c-rel组成。在前B细胞向B细胞分化过程中,p50和p65的水平没有变化,但与前B细胞相比,p75c-rel在B细胞中的丰度高5至6倍,这一发现与NF-κB亚基使用的转变一致。在脂多糖诱导的B细胞增殖过程中,核内p50同二聚体和含p75c-rel复合物的短暂上调与c-rel和p105而非p65 mRNA表达的同时增加相对应,这一发现与B细胞中rel-NF-κB的表达受自身调节机制控制一致。