Expression and Function of IL-12 and IL-18 Receptors on Human Tonsillar B Cells1

Expression and Function of IL-12 and IL-18 Receptors on Human Tonsillar B Cells1
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人扁桃体 B 细胞上 IL-12 和 IL-18 受体的表达和功能1

DOI:
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发表时间:
2000
影响因子:
4.4
通讯作者:
V. Pistoia
V. Pistoia
中科院分区:
医学2区
文献类型:
--
作者:
I. Airoldi;G. Gri;J. Marshall;A. Corcione;P. Facchetti;R. Guglielmino;G. Trinchieri;V. Pistoia

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IL-12激活鼠和人B细胞,但是关于IL-12 R在人B淋巴细胞上的表达和功能的信息很少。在这里,我们表明,后者的细胞,新鲜分离的人扁桃体,表达IL-12 R的β1和β2链的转录本和β2链mRNA的选择性增加(4- 5倍),通过与金黄色葡萄球菌科万I细菌或IL-12孵育。用IL-12刺激B细胞诱导IL-18 R的两条链的转录物的从头表达,即,IL-1受体相关蛋白和辅助蛋白样。功能研究表明,IL-12和IL-18都通过NF-κB途径向B细胞传递信号。在IL-12的情况下,没有检测到STAT转录因子,特别是STAT-4的参与。c-rel和p50是NF-κB家族成员,参与IL-12介导的信号转导至B细胞。IL-12和IL-18协同诱导扁桃体B细胞产生IFN-γ,但不刺激B细胞分化,尽管任一细胞因子促进培养上清液中IgM的分泌。最后,幼稚扁桃体B细胞(而非生发中心或记忆)被确定为诱导NF-κB活化和IFN-γ产生的唯一IL-12靶细胞。
IL-12 activates murine and human B cells, but little information is available as to the expression and function of IL-12R on human B lymphocytes. Here we show that the latter cells, freshly isolated from human tonsils, expressed the transcripts of both β1 and β2 chains of IL-12R and that β2 chain mRNA was selectively increased (4- to 5-fold) by incubation with Staphylococcus aureus Cowan I bacteria or IL-12. B cell stimulation with IL-12 induced de novo expression of the transcripts of the two chains of IL-18R, i.e., IL-1 receptor-related protein and accessory protein-like. Functional studies showed that both IL-12 and IL-18 signaled to B cells through the NF-κB pathway. In the case of IL-12, no involvement of STAT transcription factors, and in particular of STAT-4, was detected. c-rel and p50 were identified as the members of NF-κB family involved in IL-12-mediated signal transduction to B cells. IL-12 and IL-18 synergized in the induction of IFN-γ production by tonsillar B cells, but not in the stimulation of B cell differentiation, although either cytokine promoted IgM secretion in culture supernatants. Finally, naive but not germinal center or memory, tonsillar B cells were identified as the exclusive IL-12 targets in terms of induction of NF-κB activation and of IFN-γ production.
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