The roles of B cells in MRL/lpr murine lupus
The roles of B cells in MRL/lpr murine lupus
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DOI：
10.1111/j.1749-6632.1997.tb52046.x
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发表时间：
1997-01-01
期刊：
影响因子：
--
通讯作者：
Shlomchik, MJ
中科院分区：
文献类型：
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作者：
Chan, O;Madaio, MP;Shlomchik, MJ
系统性自身免疫性疾病是T细胞、B细胞和靶组织之间复杂相互作用的结果。由于这些相互作用，很难区分不同类型的细胞对启动自身免疫反应和由此导致的特定病理损害的贡献。也很难将早期事件分离出来，这无疑是一系列放大事件，部分原因是B细胞和T细胞激活之间的相互依赖。为了更好地解决这些问题，已经开发了各种狼疮小鼠遗传模型，狼疮是一种典型的人类系统性自身免疫性疾病。这些小鼠的疾病已经被仔细描述过了。虽然没有与人类SLE完全相似的小鼠模型，但它们在确定发病机制和重要细胞类型的作用方面非常有用。例如，抗体和细胞的转移使致病的自身抗体和细胞的鉴定和鉴定成为可能。抗Thy16或抗CD4Abs7的小鼠的治疗已经确立了CD4+T细胞在自身抗体的产生和疾病中的重要作用。尽管这类研究提供了丰富的信息，但它们是有限的。特别是，为了证明相关细胞的作用并更好地定义重要细胞的亚群，不可能重建受抗体抑制的动物。通过将这些小鼠狼疮模型与影响T细胞或B细胞的基因敲除突变相结合，可能会更准确地阐明T和B细胞亚群在自身免疫功能障碍中的作用及其相互作用。由于在没有外源干预的情况下，特定的细胞或分子在这样的小鼠中被消除，它们也可以在重建实验中作为受体，这大大扩展了分析的能力。在这篇手稿中，我们将总结我们在B细胞在肾炎和血管炎中的作用方面所做的工作，并将提供一些关于B细胞在自发T细胞激活中作用的新数据。
Systemic autoimmune diseases are the result of complex interactions among T cells, B cells, and target tissues. Because of these interactions, it has been difficult to distinguish the contributions of various cell types to both the initiation of the autoimmune response and the resultant specific pathologic lesions. It has also been difficult to isolate the early events in what is undoubtedly a cascade of amplifying events, in part because of the interdependence of B and T cell activation. To better address these issues, various genetic murine models of lupus, a prototypical human systemic autoimmune disease, have been developed. Disease in these mice has been carefully described. Although no murine model exactly resembles human SLE, they have been very useful in identifying the mechanisms of pathogenesis and the roles of important cell types. For example, transfer of antibodies (Abs) and cells has allowed identification and characterization of pathogenic autoantibodies and cell^.^-^ Treatment of mice with anti-Thy16 or anti-CD4 Abs7 has established important roles for CD4+ T cells in auto-Ab production and disease. Although such studies have been informative, they are limited. In particular, it is not possible to reconstitute Ab-suppressed animals in order to prove the role of the cells in question and better define subsets of important cells. By crossing these murine lupus models with knockout mutations that affect T cells or B cells, a more precise elucidation may be possible of the role of T and B cell subsets and their interactions in autoimmune dysfunction. Because specific cells or molecules are eliminated in such mice without exogenous intervention, they can also serve as recipients in reconstitution experiments, which greatly extend the power of the analysis. In this manuscript, we will summarize our own work using this approach on the role of B cells in nephritis and vasculitis and will present some new data on the role of B cells in spontaneous T cell activation.