自身免疫
自身免疫性疾病
B细胞
免疫学
边缘地带
生物
断点群集区域
系统性红斑狼疮
脾脏
肾脏疾病
受体
疾病
内分泌学
抗体
内科学
遗传学
医学
作者
Randall F. Gill,Patricia Mathieu,Lawrence H. Lash,Allen J. Rosenspire
标识
DOI:10.1093/toxsci/kfad120
摘要
Autoimmune diseases are multifactorial and include environmental as well as genetic drivers. Although much progress has been made in understanding the nature of genetic underpinnings of autoimmune disease, by comparison much less is understood regarding how environmental factors interact with genetics in the development of autoimmunity and autoimmune disease. In this report, we utilize the (NZB X NZW) F1 mouse model of Systemic Lupus Erythematosus (SLE). Mercury is a xenobiotic that is environmentally ubiquitous and is epidemiologically linked with the development of autoimmunity. Among other attributes of human SLE, (NZB X NZW) F1 mice spontaneously develop autoimmune-mediated kidney disease. It has been previously shown that if (NZB X NZW) F1 mice are exposed to inorganic mercury (Hg2+), the development of autoimmunity, including autoimmune kidney pathology, is accelerated. We now show that in these mice the development of kidney disease is correlated with a decreased percentage of marginal zone (MZ) B cells in the spleen. In Hg2+-intoxicated mice, kidney disease is significantly augmented, and matched by a greater decrease in MZ B cell splenic percentages than found in control mice. In Hg2+- intoxicated mice, the decrease in MZ B cells appears to be linked to aberrant B Cell Receptor (BCR) signal strength in transitory 2 (T2) B cells, developmental precursors of MZ B cells.
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