Abnormal B cell signal transduction in systemic lupus erythematosus.
Abnormal B cell signal transduction in systemic lupus erythematosus.
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DOI：
10.1159/000066857
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
I. Khan;G. Tsokos;G. Kammer
中科院分区：
文献类型：
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作者：
I. Khan;G. Tsokos;G. Kammer
B 细胞和 B 细胞/T 细胞相互作用在系统性红斑狼疮 (SLE) 的病理生理学中发挥着关键作用。与 SLE 中的循环 T 细胞池相反，B 细胞数量并未减少。事实上，B 细胞的增殖速度加快，并自发分泌更多量的免疫球蛋白 (Ig)，包括针对自身核、自身细胞质和自身质膜自身抗原 (autoAg) 的自身抗体 (autoAb)。在这一系列的自身抗体中，抗核自身抗体针对离散的核自身抗原，通过荧光显微镜观察可产生特征性的免疫荧光模式[1-4]。这些自身抗体的直接致病作用已被证明至少对某些自身抗体具有直接致病作用，例如抗双链 DNA、抗 Ro 和抗磷脂自身抗体 [5]。除了分泌致病性自身抗体外，最近的证据还为 B 细胞在形成免疫库中的作用提供了病理生理学相关的见解，从而指出了 B 细胞可能促进 SLE 免疫发病机制的新方式。 SLE B 细胞似乎有一种内在的紊乱，导致了通常所说的“多动症”。该术语指的是多种异常功能，例如增殖和 Ig 合成增强，最终导致高丙种球蛋白血症。本章将重点关注已发现的导致细胞过度活跃的 SLE B 细胞信号通路异常。由于对人类和小鼠 SLE B 细胞异常信号传导的了解仍然非常有限，因此我们的主要目标是比较生理 B 细胞信号传导机制
B cells and B cell/T cell interactions play a key role in the pathophysiology of systemic lupus erythematosus (SLE). In contrast to the circulating T cell pool in SLE, B cells are not numerically decreased. Indeed, B cells have a heightened rate of proliferation and spontaneously secrete increased amounts of immunoglobulins (Ig), including autoantibodies (autoAbs) directed against self-nuclear, self-cytoplasmic, and self-plasma membrane autoantigens (autoAgs). Among this panoply of autoAbs, antinuclear autoAbs are directed against discrete nuclear autoAgs that result in characteristic immunofluorescent patterns by fluorescence microscopy [1–4]. A direct pathogenic role of these autoAbs has been demonstrated for at least some, such as anti-double-stranded DNA, anti-Ro and antiphospholipid autoAbs [5]. Besides secreting pathogenic autoAbs, recent evidence has provided pathophysiologically relevant insights into the role of B cells in shaping the immune repertoire, thereby pointing to new ways in which B cells may contribute to the immunopathogenesis of SLE. SLE B cells appear to have an intrinsic disorder that contributes to what has been generally termed ‘hyperactivity’. This term refers to diverse, abnormal functions, such as proliferation and augmented Ig synthesis, which culminate in hypergammaglobulinemia. This chapter will focus on the identified abnormalities of the SLE B cellsignaling pathway that contribute to the cell’s hyperactivity. Because knowledge of abnormal signaling in both human and murine SLE B cells is still very limited, our principal goal will be to compare physiologic B cell signaling mechanisms