Chan O T, Madaio M P, Shlomchik M J
Section of Immunobiology, Yale University School of Medicine, New Haven 06510, USA.
Immunol Rev. 1999 Jun;169:107-21. doi: 10.1111/j.1600-065x.1999.tb01310.x.
A standard view of B cells in systemic autoimmunity is that they promote lupus by producing autoantibodies (autoAb). However, this view is incomplete because recent studies have revealed that autoimmune disease can be dissociated from autoAb deposition. Furthermore, the spontaneous T-cell activation and organ infiltration in systemic lupus erythematosus patients and animal models are difficult to explain entirely via a direct autoAb-mediated mechanism. In this review, we describe work addressing the B-cell functions of autoantigen presentation and autoAb production in lupus pathogenesis. In the JHD-MRL-Faslpr strain (JHD/lpr), a B-cell-deficient version of the lupus-prone MRL-Faslpr (MRL/lpr) mouse, spontaneous nephritis and dermatitis is abrogated, demonstrating that B cells have a primary role in disease. B cells play a similar role in Fas-intact, lupus-prone MRL mice. To address the role of autoantigen presentation, we analyzed transgenic mice which have B cells that cannot secrete immunoglobulin (mIgM transgenic mice). The restoration of B cells without antibody caused substantial interstitial nephritis and vasculitis although less marked than the intact MRL/lpr controls. To address the role of autoAb, we infused serum from aged MRL/lpr mice into JHD/lpr mice. At most, mild to no nephritis was observed in the infused mice. These results indicate that B cells are promoting autoimmunity in mechanisms other than autoAb secretion, and we describe a model depicting these B-cell roles in the context of other inflammatory events in lupus.
系统性自身免疫中对B细胞的一种标准观点是，它们通过产生自身抗体（autoAb）来促进狼疮。然而，这种观点并不完整，因为最近的研究表明，自身免疫性疾病可以与自身抗体沉积相分离。此外，系统性红斑狼疮患者和动物模型中自发的T细胞活化和器官浸润很难完全通过直接的自身抗体介导机制来解释。在这篇综述中，我们描述了关于狼疮发病机制中自身抗原呈递和自身抗体产生的B细胞功能的研究工作。在JHD-MRL-Faslpr品系（JHD/lpr）中，即狼疮易感MRL-Faslpr（MRL/lpr）小鼠的B细胞缺陷版本，自发性肾炎和皮炎被消除，这表明B细胞在疾病中起主要作用。B细胞在Fas完整的狼疮易感MRL小鼠中也发挥类似作用。为了研究自身抗原呈递的作用，我们分析了具有不能分泌免疫球蛋白的B细胞的转基因小鼠（mIgM转基因小鼠）。没有抗体的B细胞的恢复导致了大量的间质性肾炎和血管炎，尽管不如完整的MRL/lpr对照组明显。为了研究自身抗体的作用，我们将老年MRL/lpr小鼠的血清注入JHD/lpr小鼠体内。在注入血清的小鼠中，最多观察到轻度至无肾炎。这些结果表明，B细胞通过自身抗体分泌以外的机制促进自身免疫，并且我们描述了一个模型，描绘了这些B细胞在狼疮其他炎症事件背景下的作用。
