Beta transforming growth factors are potential regulators of B lymphopoiesis.

Beta transforming growth factors are potential regulators of B lymphopoiesis.
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DOI:
10.1084/jem.166.5.1290
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发表时间:
1987-11-01
影响因子:
15.3
通讯作者:
KINCADE, PW
KINCADE, PW
中科院分区:
医学1区
文献类型:
--
作者:
LEE, G;ELLINGSWORTH, LR;GILLIS, S;WALL, R;KINCADE, PW

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发现多肽的转化生长因子β(TGF-β)家族的成员是正常骨髓衍生的和转化的克隆前B细胞上κ轻链表达的有效体外抑制剂,以及这些细胞对有丝分裂原反应性的成熟的有效体外抑制剂。TGF-β的抑制是选择性的,因为Ia表达不被阻断。与LPS、IL- 1、NZB血清因子、IL-4和IFN-γ优先诱导前B细胞系上的κ或Ia或两者的观察结果一起,这些结果进一步表明,IG和II类分子的获得是由不同的拮抗剂以及激动剂独立控制的。此外,IFN-γ诱导的κ链似乎对TGF-β下调不像其他测试因子刺激的那样敏感,这增加了同一基因激活可能来自不同跨膜信号传导途径的可能性。与TGF-β对前B细胞获得κ的抑制作用和对成熟B细胞暴露于LPS后κ增加的抑制作用相反,如通过κ RNA水平和/或表面荧光测量的,在未刺激的脾B细胞或组成性产生κ的两种克隆B细胞系上未观察到抑制作用。因此,TGF-β可能在B细胞分化的特定阶段通过抑制Ig基因的起始或增加Ig基因的转录而起作用,并且因此可能是B淋巴细胞生成的重要负调节因子。这是第一个发现具有这种效果的天然物质。
Members of the transforming growth factor beta (TGF-beta) family of polypeptides were found to be potent in vitro inhibitors of kappa light chain expression on normal bone marrow-derived and transformed cloned pre-B cells, and of the maturation of these cells to mitogen responsiveness. The inhibition by TGF-beta was selective in that Ia expression was not blocked. Together with the observations that LPS, IL- 1, NZB serum factors, IL-4, and IFN-gamma preferentially induced either kappa or Ia, or both, on a pre-B cell line, these results further suggest that acquisition of Ig and class II molecules is independently controlled by different antagonists as well as agonists. In addition, kappa chain induction by IFN-gamma does not appear to be as sensitive to TGF-beta downregulation as that stimulated by other factors tested, and this raises the possibility that activation of the same gene may result from different transmembrane signaling pathways. In contrast to the inhibitory effects of TGF-beta on kappa acquisition by pre-B cells and on kappa increase after exposure of mature B cells to LPS, as measured by kappa RNA levels and/or surface fluorescence, no inhibition was observed on unstimulated spleen B cells or on two cloned B cell lines that constitutively produce kappa. Thus, TGF-beta may function during specific stages of B cell differentiation by inhibiting initiation of, or increased transcription of Ig genes, and therefore, may be an important negative regulator of B lymphopoiesis. It is the first natural substance found to have this effect.
DOI: 10.1084/jem.163.4.938
发表时间: 1986-04-01
影响因子: 15.3
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