Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM
Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM
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DOI：
10.1073/pnas.97.3.1184
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发表时间：
2000-02-01
影响因子：
11.1
通讯作者：
Chen, JZ
中科院分区：
文献类型：
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作者：
Boes, M;Schmidt, T;Chen, JZ
患有系统性红斑狼疮和类风湿性关节炎的个体的特征在于存在高水平的循环IgM和IgG自身抗体。虽然IgG自身抗体通常是致病性的，但IgM自身抗体在自身免疫性疾病中的作用尚不清楚。使用小鼠不能分泌IgM，但能够表达表面IgM和IgD，并分泌其他类别的免疫球蛋白，我们研究了缺乏分泌的IgM的IgG自身抗体和自身免疫性疾病的发展中的狼疮倾向的淋巴组织增生性（IPR）小鼠的影响。与常规的Ipr小鼠相比，缺乏分泌型IgM的Ipr小鼠产生了高水平的IgG自身抗体，以对抗双链DNA和组蛋白，并在肾小球中沉积了更丰富的免疫复合物;它们也遭受了更严重的肾小球肾炎，并在更早的年龄死于这种疾病。类似地，分泌IgM的缺乏也导致正常小鼠中IgG自身抗体的加速发展。这些发现表明，分泌的IgM，包括IgM自身抗体产生的天然或作为自身免疫反应的一部分，可能会减轻与IgG自身抗体相关的自身免疫病理的严重程度。
Individuals with systemic lupus erythematosus and rheumatoid arthritis are characterized by the presence of high levels of circulating IgM and IgG autoantibodies. Although IgG autoantibodies often are pathogenic, the role of IgM autoantibodies in autoimmune disease is not clear. Using mice that are unable to secrete IgM but are able to express surface IgM and IgD and to secrete other classes of immunoglobulins, we examined the effect of the absence of secreted IgM in the development of IgG autoantibodies and autoimmune disease in lupus-prone lymphoproliferative (Ipr) mice. Compared with regular Ipr mice, Ipr mice that lack secreted IgM developed elevated levels of IgG autoantibodies to double-stranded DNA and histones and had more abundant deposits of immune complexes in the glomeruli; they also suffered more severe glomerulonephritis and succumbed to the disease at an earlier age. Similarly, the absence of secreted IgM also resulted in an accelerated development of IgG autoantibodies in normal mice. These findings suggest that secreted IgM, including IgM autoantibodies produced naturally or as part of an autoimmune response, may lessen the severity of autoimmune pathology associated with IgG autoantibodies.