Erythrocyte Saturation with IgG Is Required for Inducing Antibody-Mediated Immune Suppression and Impacts Both Erythrocyte Clearance and Antigen-Modulation Mechanisms
Erythrocyte Saturation with IgG Is Required for Inducing Antibody-Mediated Immune Suppression and Impacts Both Erythrocyte Clearance and Antigen-Modulation Mechanisms
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DOI：
10.4049/jimmunol.1700874
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发表时间：
2018-02-15
影响因子：
4.4
通讯作者：
Lazarus, Alan H.
中科院分区：
文献类型：
--
作者：
Cruz-Leal, Yoelys;Marjoram, Danielle;Lazarus, Alan H.
抗- d可以预防胎儿和新生儿的溶血性疾病，这种机制被称为抗体介导的免疫抑制（AMIS）。Anti-D，以及其他诱导amis的多克隆抗体，最常诱导表位掩蔽和红细胞清除机制。我们之前观察到，一些成功诱导AMIS效应的抗体可以分为介导表位掩蔽的抗体和诱导红细胞清除的抗体，从而能够分别分析这些机制。此外，amis诱导活性最近已被证明可诱导银调节（红细胞表面银损失）。为了评估这些机制，我们用转基因小鼠红细胞免疫小鼠，这些小鼠红细胞表达一种由鸡蛋溶菌酶、含有aa 251-349的OVA序列和人Duffy跨膜蛋白（HOD-Ag）组成的重组Ag蛋白，并使用系列剂量的多克隆抗OVA IgG作为诱导AMIS的抗体。抗OVA抗体在没有明显表位屏蔽的情况下诱导AMIS。ami仅在红细胞IgG饱和时发生。这种Ab能够诱导HOD-RBC清除，以及在引起AMIS效应的Ab剂量下OVA表位的丢失。hod - rbc也失去了对鸡蛋溶菌酶和Duffy部分Ag特异性抗体的反应性，这与Ag调节和/或胞浆形成机制的启动一致。这些数据支持这样一个概念，即不引起表位掩蔽的诱导AMIS的Ab可以以与RBC清除和/或Ag调制一致的方式诱导AMIS效应。
Anti-D prevents hemolytic disease of the fetus and newborn, and this mechanism has been referred to as Ab-mediated immune suppression (AMIS). Anti-D, as well as other polyclonal AMIS-inducing Abs, most often induce both epitope masking and erythrocyte clearance mechanisms. We have previously observed that some Abs that successfully induce AMIS effects could be split into those that mediate epitope masking versus those that induce erythrocyte clearance, allowing the ability to analyze these mechanisms separately. In addition, AMIS-inducing activity has recently been shown to induce Ag modulation (Ag loss from the erythrocyte surface). To assess these mechanisms, we immunized mice with transgenic murine RBCs expressing a single Ag protein comprising a recombinant Ag composed of hen egg lysozyme, OVA sequences comprising aa 251-349, and the human Duffy transmembrane protein (HOD-Ag) with serial doses of polyclonal anti-OVA IgG as the AMIS-inducing Ab. The anti-OVA Ab induced AMIS in the absence of apparent epitope masking. AMIS occurred only when the erythrocytes appeared saturated with IgG. This Ab was capable of inducing HOD-RBC clearance, as well as loss of the OVA epitope at doses of Ab that caused AMIS effects. HOD-RBCs also lost reactivity with Abs specific for the hen egg lysozyme and Duffy portions of the Ag consistent with the initiation of Ag modulation and/or trogocytosis mechanisms. These data support the concept that an AMIS-inducing Ab that does not cause epitope masking can induce AMIS effects in a manner consistent with RBC clearance and/or Ag modulation.