B cell activation induced by superantigens

超抗原诱导 B 细胞活化

• 批准号: 06807047
• 负责人: SHIRAI Akira
• 金额: $ 1.22万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06807047/
• 关键词: Superantigens; B cell activation; MHC Class II; Macrophage; Immunoglobulin; IL-6; MCP-1; Autoimmunity; MHCクラスII; MHCクラスII分子; MHCクラスIIリガンド; マクロファージ活性化

It is now widely accepted that superantigens (SAgs), by binding to TCR Vb elements on T cells and to MHC class II molecules on accessory cells, stimulate T cells expressing particular TCR Vb chains. As SAg-activated T cells, having wide variety of antigen specificities, are supposed to be polyclonal by nature, they may then induce the activation of polyclonal B cells including autoreactive B cells. This possibility is now providing a basis for the hypothesis that SAgs may play important roles in the induction of autoimmune diseases.Theoretically there are two possible mechanisms by which B cells might be polyclonally activated by SAgs ; first, SAgs stimulate B cells directly by acting as MHC class II ligands. Second, as mentioned above, SAgs stimulate B cells indirectly by virtue of their ability to mediate T/B interaction.We first examine the direct effect of SAgs on accessory cells. The experiments using mouse macrophage cell lines and human B cell lines showed that certain bacrerial SAgs stimulated directly macrophages and B cells to secrete cytokines but that all bacterial SAgs tested inhibited Ig secretion from B cells. Next, we examine the net-effects including the direct and indirect actions of SAgs on B Cell activation. The experiments using unseparated human PBMC showed that bacterial SAg stimulated B cells to secrete Ig transienty in the early phase (3 days post stimulation) but finally inhibited the secretion by 7 days post stimulation.In conclusion, although there still remains the possibility that superantigens may activate particular types of autoreactive B cells by specific activation of autoreactive T cells, it seems unlikely that autoreactive B cells can be activated by the mechanism of polyclonal B cell activation directly or indirectly induced by SAg stimulation.

目前人们普遍认为，超抗原(SAG)通过与T细胞上的TCR VB元件和辅助细胞上的MHC II类分子结合，刺激T细胞表达特定的TCR VB链。由于SAG激活的T细胞具有广泛的抗原特异性，本质上被认为是多克隆的，因此它们可能会诱导包括自身反应性B细胞在内的多克隆B细胞的激活。这种可能性现在为SAGS可能在自身免疫性疾病的诱导中发挥重要作用的假说提供了基础。理论上，SAGS可能通过两种可能的机制来激活B细胞：第一，SAGS作为MHC II类配体直接刺激B细胞。第二，如上所述，SAGS通过其调节T/B相互作用的能力间接刺激B细胞。我们首先研究SAGS对辅助细胞的直接影响。用小鼠巨噬细胞系和人B细胞系进行的实验表明，某些菌落直接刺激巨噬细胞和B细胞分泌细胞因子，而所有受试的细菌凹陷都抑制B细胞分泌Ig。接下来，我们考察SAGS对B细胞激活的网络效应，包括直接和间接作用。使用未分离的人PBMC的实验表明，细菌SAG在刺激早期(刺激后3d)刺激B细胞短暂地分泌Ig，但在刺激后7d最终抑制其分泌。结论：尽管超抗原仍有可能通过自身反应性T细胞的特异性激活来激活特定类型的自身反应性B细胞，但似乎不太可能通过SAG刺激直接或间接诱导多克隆B细胞激活的机制来激活自身反应性B细胞。