Systemic lupus erythematosus (SLE) is characterized by high levels of autoantibodies and multiorgan tissue damage. The pathogenesis of splenomegaly in SLE remains unknown. In this study, the role of immunoglobulin G (IgG) generation and deposition in the inflammation of the spleen and associated dysfunction in SLE was investigated. In the lupus mice, we observed the development of spontaneous splenomegaly, and we found that lupus serum IgG is an important pathological factor involved in the initiation of inflammation and further germinal center (GC) and plasma cell formation. We discovered that macrophages of the splenic marginal zone are dispensable for the GC response induced by lupus IgG, but red pulp macrophages are important for GC responses. Furthermore, we found that pathogenic lupus IgG promotes inflammation and GC formation through the macrophage-mediated secretion of TNF-α. Syk inhibitor treatment suppressed the changes in the histopathology of the spleen induced by lupus IgG. This study will contribute to the understanding of the pathogenesis of splenomegaly in lupus and promote the development of an effective therapeutic strategy for SLE.

中文翻译：

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免疫球蛋白G在鼠狼疮脾肿大发病机理中的主要作用。

系统性红斑狼疮（SLE）的特点是高水平的自身抗体和多器官组织损伤。SLE脾肿大的发病机制仍然未知。在这项研究中，研究了免疫球蛋白G（IgG）的生成和沉积在脾脏炎症和SLE中相关功能障碍中的作用。在狼疮小鼠中，我们观察到自发性脾肿大的发展，并且我们发现狼疮血清IgG是重要的病理因素，参与炎症的引发以及进一步的生发中心（GC）和浆细胞的形成。我们发现脾脏边缘区的巨噬细胞对于狼疮IgG诱导的GC反应是必不可少的，但红髓巨噬细胞对于GC反应很重要。此外，我们发现，致病性狼疮IgG通过巨噬细胞介导的TNF-α分泌促进炎症和GC的形成。Syk抑制剂治疗抑制了狼疮IgG诱导的脾组织病理学变化。这项研究将有助于了解狼疮脾肿大的发病机理，并促进开发一种有效的SLE治疗策略。