Interleukin 6 induces secretion of IgG1 by coordinated transcriptional activation and differential mRNA accumulation.
Interleukin 6 induces secretion of IgG1 by coordinated transcriptional activation and differential mRNA accumulation.
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白细胞介素 6 通过协调转录激活和差异 mRNA 积累诱导 IgG1 分泌。
DOI：
10.1073/pnas.86.20.8024
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发表时间：
1989
影响因子：
11.1
通讯作者：
Chen-Kiang,S
中科院分区：
文献类型：
--
作者：
Raynal,MC;Liu,ZY;Hirano,T;Mayer,L;Kishimoto,T;Chen-Kiang,S
白细胞介素6（IL-6）诱导终末分化的B细胞的分子机制进行了研究，在一个亚群的克隆人B-淋巴母细胞样细胞系ESS选择高密度的细胞表面IgG 1。用IL-6诱导CESS细胞导致分泌的特异性γ 1（γ 1 s）mRNA的15倍优先积累，但不是交替处理的膜特异性γ 1（γ 1 m）mRNA。同样，微秒mRNA，但不是微米mRNA的nonproductively重排μ重链等位基因也增加了。伴随着γ 1 s mRNA的差异积累，λ轻链mRNA增加了4.5倍，导致IgG 1的分泌。在分离的细胞核中的转录分析表明，转录激活是免疫球蛋白mRNA定量增加的主要机制（γ 1和μ为5.5倍，λ为至少2倍）。由于聚合酶加载在到达CESS细胞中的下游γ 1 m多聚腺苷酸化位点之前减少了75%，与IL-6诱导无关，转录暂停/终止似乎是内在的，并且有助于活化B细胞中γ 1 s和γ 1 m多聚腺苷酸化位点的选择。此外，差异mRNA稳定性可能有助于在IL-6诱导下γ 1 s/γ 1 m mRNA比率的改变。
The molecular mechanism by which interleukin 6 (IL-6) induces terminal differentiation of B cells was investigated in a subpopulation of the clonal human B-lymphoblastoid cell line CESS selected for high density of cell surface IgG1. Induction of CESS cells with IL-6 resulted in a 15-fold preferential accumulation of secreted-specific gamma 1 (gamma 1s) mRNA but not of the alternatively processed membrane-specific gamma 1 (gamma 1m) mRNA. Similarly, microseconds mRNA but not the microns mRNA of the nonproductively rearranged mu heavy-chain allele was also increased. Accompanying the differential accumulation of gamma 1s mRNA was a 4.5-fold increase in lambda light-chain mRNA, leading to secretion of IgG1. Analyses of transcription in isolated nuclei demonstrated that transcriptional activation was the primary mechanism for quantitative increase of immunoglobulin mRNAs (5.5-fold for gamma 1 and mu and at least 2-fold for lambda). Since polymerase loading is diminished by 75% before reaching the downstream gamma 1m polyadenylylation site in CESS cells, irrespective of IL-6 induction, transcriptional pausing/termination appears intrinsic and contributes to the selection of gamma 1s and gamma 1m polyadenylylation sites in activated B cells. Furthermore, differential mRNA stabilization is likely to contribute to the alteration of the gamma 1s/gamma 1m mRNA ratio at IL-6 induction.