B cell activation induced by superantigens

现在广泛接受的是，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，刺激表达特定TCR Vb链的T细胞。由于SAg活化的T细胞具有广泛的抗原特异性，被认为本质上是多克隆的，因此它们可以诱导包括自身反应性B细胞在内的多克隆B细胞的活化。理论上讲，SAgs多克隆激活B细胞可能有两种机制：第一，SAgs作为MHC II类配体直接刺激B细胞;第二，如上所述，SAgs通过介导T/B相互作用的能力间接刺激B细胞。使用小鼠巨噬细胞系和人B细胞系的实验表明，某些细菌SAg直接刺激巨噬细胞和B细胞分泌细胞因子，但所有测试的细菌SAg都抑制B细胞的IG分泌。接下来，我们研究了包括SAgs对B细胞活化的直接和间接作用的净效应。用未分离的人PBMC进行的实验表明，细菌SAg在早期刺激B细胞瞬时分泌IG（刺激后3天），但最终在刺激后7天抑制分泌。总之，尽管仍然存在超抗原可以通过特异性激活自身反应性T细胞来激活特定类型的自身反应性B细胞的可能性，自身反应性B细胞似乎不太可能通过由SAg刺激直接或间接诱导的多克隆B细胞活化机制而被活化。

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.