IL-12 and IL-18 down-regulate B cell migration in an Ly49D-dependent manner
IL-12 and IL-18 down-regulate B cell migration in an Ly49D-dependent manner
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DOI：
10.1002/eji.200737083
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发表时间：
2007-07-01
影响因子：
5.4
通讯作者：
Shachar, Idit
中科院分区：
文献类型：
--
作者：
Hart, Gili;Flaishon, Liat;Shachar, Idit
为了完成成熟并参与体液免疫反应，离开骨髓的未成熟 B 细胞被靶向脾脏中的特定区域，并在那里分化为成熟细胞。此前，我们发现未成熟的 B 细胞主动下调整合素介导的向淋巴结或炎症部位的迁移，从而使其能够靶向脾脏。这种抑制是由 IFN-γ 介导的，这些未成熟的 B 细胞以低水平转录和分泌 IFN-γ。 B 细胞成熟后其表达随后下调。激活性和抑制性 MHC I 类受体 Ly49D 和 Ly49G2 调节 B 细胞中 IFN-γ 的分泌，防止它们迁移到抗原富集位点以及过早遇到抗原，同时使它们能够在成熟时进入 LN。在本研究中，我们阐明了 Ly49 受体调节 IFN-γ 水平的途径。我们发现 Ly49D 刺激会触发信号级联，从而增加 IL-12B 和 IL-18 的转录；这些反过来又可以与其特定受体相互作用，这些受体在未成熟 B 细胞上表达水平升高。 IL-12B 和 IL-18 受体的连接诱导 IFN-γ 的分泌，从而调节其细胞骨架重排和迁移。
In order to complete their maturation and participate in the humoral immune response, immature B cells that leave the bone marrow are targeted to specific areas in the spleen, where they differentiate into mature cells. Previously, we showed that immature B cells actively down-regulate their integrin-mediated migration to LN or to sites of inflammation, enabling their targeting to the spleen. This inhibition is mediated by IFN-gamma, which is transcribed and secreted at low levels by these immature B cells; its expression is subsequently down-regulated following B cell maturation. The activating and inhibitory MHC class I receptors, Ly49D and Ly49G2, regulate IFN-gamma secretion in B cells, preventing their migration to antigen-enriched sites and their premature encounter with an antigen, while enabling their entry into the LN when mature. In the present study, we elucidate the pathways by which the Ly49 receptors regulate IFN-gamma levels. We show that Ly49D stimulation triggers a signaling cascade that increases transcription of both IL-12B and IL-18; these, in turn, can interact with their specific receptors, which are expressed at elevated levels on immature B cells. Ligation of the IL-12B and IL-18 receptors induces the secretion of IFN-gamma, thereby regulating their cytoskeleton rearrangement and migration.