Human polyreactive IgM monoclonal antibodies with blocking activity against self-reactive IgG
Human polyreactive IgM monoclonal antibodies with blocking activity against self-reactive IgG
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DOI：
10.1046/j.1365-3083.1997.d01-418.x
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发表时间：
1997-04-01
影响因子：
3.7
通讯作者：
Sanchez, B
中科院分区：
文献类型：
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作者：
Melero, J;Tarrago, D;Sanchez, B
已发现天然 IgM 抗体参与正常血清中 IgG 反应性的控制。作者研究了来自三名肾透析患者血液样本 B 细胞的四种人 IgM 单克隆抗体（BY-2、BY-7、BY-10 和 IRM-7）的阻断活性，这些抗体显示出与天然多反应性自身抗体相似的多特异性特性。为了实现这一目标，使用这些 MoAb 对从健康对照、三名 SLE 患者和两名自身免疫性甲状腺炎患者纯化的 IgG 与组蛋白、dsDNA、RNP 和甲状腺球蛋白的结合进行竞争性抑制测定。 MoAb 抑制自身反应性 IgG 与组蛋白和 dsDNA 的结合，但不抑制自然和活性或非活性期疾病相关自身反应性 IgG 与甲状腺球蛋白或 RNP 的结合。 MoAb 的抑制作用是通过与自身反应性 IgG 的 V 区依赖性相互作用介导的，如这些 MoAb 阻断自身反应 IgG 的 F(ab')(2) 片段与抗原（组蛋白和 dsDNA）结合的能力所示。自身抗体活性的阻断呈剂量依赖性，在患者 IgG 和给定 MoAb 之间的特定摩尔比时出现最大抑制。相比之下，MoAb 不会抑制四名多次输血肾透析患者血清中存在的 IgG 同种抗体与不同细胞表面的靶抗原的结合。这些结果支持调节自身免疫反应的功能性独特型网络的概念，并表明所研究的 IgM MoAb 可能是天然多反应性抗体，属于具有高度连接的 V 区的自身抗体生理网络，能够结合和功能性中和天然和病理性自身抗体的 V 区。
Natural IgM antibodies have been found to be involved in the control of IgG reactivity in normal serum. The authors investigated the blocking activity of four human IgM monoclonal antibodies (BY-2, BY-7, BY-10 and IRM-7) derived from B-cells from blood samples of three renal dialysis patients, which had shown multispecific properties similar to those observed for natural polyreactive autoantibodies. To achieve this, competitive inhibition assays were performed with these MoAbs on the binding of IgG purified from a healthy control, three patients with SLE, and two patients with autoimmune thyroiditis, to histone, dsDNA, RNP and thyroglobulin. MoAbs inhibited binding of self-reactive IgG to histone and dsDNA, but not to thyroglobulin or RNP, of natural and active or inactive phase disease-associated autoreactive IgG. The inhibitory effect of the MoAbs was mediated by V-region dependent interactions with autoreactive IgG, as shown by the ability of these MoAbs to block the binding of F(ab')(2) fragments of autoreactive IgG to antigens (histone and dsDNA), The blocking of autoantibody activity was dose-dependent with maximal inhibition occurring at a specific molar ratio between the patient's IgG and a given MoAb. In contrast, MoAbs did not inhibit binding of IgG alloantibodies present in the sera of four polytransfused renal dialysis patients to target antigens on the surface of different cells. These results support the concept of a functional idiotypic network regulating autoimmune responses, and suggest that the IgM MoAbs under study may be natural polyreactive antibodies belonging to the physiological network of autoantibodies with highly connected V-regions, capable of binding and functionally neutralizing V-regions of natural and pathologic autoantibodies.