並列タイトル等Extensively reorganized systemic lymph nodes provide a feasible environment for self-reactivity in lupus-prone NZB/NZW F1 mice
NZBWF1マウスにおいて大規模に組織再編された全身のリンパ節が自己免疫応答に適した環境を与える
一般注記Lymphadenopathy is a frequently observed symptom in systemic lupus erythematosus, although the immunological role of lymph nodes (LNs) in systemic autoimmunity remains largely unknown. Here, we performed comprehensive and systematic analyses of LNs in lupus-prone NZB × NZW F1 (BWF1) mice, demonstrating extensive tissue reorganization of the systemic LNs with follicular expansion, hyper germinal center (GC) formation, atrophy of the paracortical T cell area, and expansion of the medulla in aged BWF1 mice bearing glomerulonephritis. The proportion of B cells was significantly increased in these reactive LNs but not in the spleen, and lymphocyte subsets involved in antibody production, i.e., GC B cells, follicular helper T cells, and plasma cells, were elevated. Draining LNs of the affected organs, such as the renal and cervical nodes, showed enhanced tissue reorganization and accumulation of effector lymphocytes, suggesting the presence of a positive feedback loop of regional responses. LN cells isolated from disease-bearing animals produced anti-DNA antibody, indicating activation of autoreactive lymphocytes in situ. The substantial development of disease and LN alterations in mice that received a splenectomy at a young age points to the importance of other secondary lymphoid organs, most likely LNs, for the progression of autoimmune responses independent of the spleen. Taken together, our findings highlight the value of taking LN alterations and activities into consideration for understanding the pathogenesis of systemic autoimmunity.
学位の種類: 博士（医学）. 報告番号: 甲第4412号. 学位記番号: 新大院博（医）甲第811号. 学位授与年月日: 平成30年3月23日
International Immunology. 2017, 29(12), 567-579. Article first published online: 30 November 2017.
新大院博（医）甲第811号
開始ページ : 1
終了ページ : 17
DOIinfo:doi/10.1093/intimm/dxx066
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