B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis
B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis
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DOI：
10.2353/ajpath.2006.060205
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发表时间：
2006-09-01
影响因子：
6
通讯作者：
Tedder, Thomas F.
中科院分区：
文献类型：
--
作者：
Hasegawa, Minoru;Hamaguchi, Yasuhito;Tedder, Thomas F.
系统性硬化症（硬皮病）是一种以皮肤中细胞外基质过度沉积为特征的自身免疫性疾病。B淋巴细胞在疾病发展或进展中的直接作用仍然存在争议，尽管自身抗体的产生是这种疾病的一个特征。为了解决这一问题，在疾病发展之前（出生后第3天）和之后（第56天），使用抗小鼠CD 20单克隆抗体消除循环和组织B细胞后，在紧皮小鼠（人类系统性硬化症的遗传模型）中评估皮肤硬化和自身免疫。CD 20单克隆抗体处理（10 - 20图）分别在第56天和第112天耗尽新生和成年紧皮小鼠中的大部分（85 - 99%）循环和组织B细胞。新生皮肤紧绷小鼠的B细胞耗竭显著抑制（约43%）皮肤纤维化、自身抗体产生和高丙种球蛋白血症的发展。B细胞耗竭也恢复了皮肤中Th 1和Th 2细胞因子mRNA表达之间更正常的平衡。相比之下，B细胞耗竭不影响皮肤纤维化，高丙种球蛋白血症，和自身抗体水平在成年小鼠与建立的疾病。因此，在疾病发作期间B细胞耗竭抑制皮肤纤维化，表明B细胞有助于在紧皮小鼠中引发系统性硬化症发病机制，但不是疾病维持所需的。
Systemic sclerosis (scleroderma) is an autoimmme disease characterized by excessive extracellular matrix deposition in the skin. A direct role for B lymphocytes in disease development or progression has remained controversial, although autoantibody production is a feature of this disease. To address this issue, skin sclerosis and autoimmunity were assessed in tight-skin mice, a genetic model of human systemic sclerosis, after circulating and tissue B-cell depletion using an anti-mouse CD20 monoclonal antibody before (day 3 after birth) and after disease development (day 56). CD20 monoclonal antibody treatment (10 to 20 fig) depleted the majority (85 to 99%) of circulatig and tissue B cells in newborn and adult tight-skin mice by days 56 and 112, respectively. B-cell depletion in newborn tight-skin mice significantly suppressed (similar to 43%) the development of skin fibrosis, autoantibody production, and hypergammaglobulinemia. B-cell depletion also restored a more normal balance between Th1 and Th2 cytokine mRNA expression in the skin. By contrast, B-cell depletion did not affect skin fibrosis, hypergammaglobulinemia, and autoantibody levels in adult mice with established disease. Thereby, B-cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance.