Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans
Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans
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DOI：
10.1093/intimm/dxg018
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发表时间：
2003-02-01
影响因子：
4.4
通讯作者：
Ober, RJ
中科院分区：
文献类型：
--
作者：
Ward, ES;Zhou, JC;Ober, RJ
免疫球蛋白是血清中含量最丰富的抗体，是体液免疫反应的重要组成部分。已知‘新生儿’Fc受体(FcRN)作为一种保护性受体，结合和挽救免疫球蛋白的降解，在维持血清免疫球蛋白水平不变方面发挥作用。然而，涉及血清免疫球蛋白稳态的细胞机制却知之甚少。在目前的研究中，我们通过分析与FcRN具有不同亲和力的免疫球蛋白分子在人内皮细胞内的命运来解决这个问题。研究表明，不与FcRN结合的免疫球蛋白在溶酶体途径中积累，为此类抗体在血清中持续时间较短提供了细胞解释。我们还研究了动态平衡系统的饱和性，发现它的容量有限。我们的观察结果直接关系到对免疫球蛋白缺乏症的认识和治疗，以及治疗性抗体的有效应用。
IgG is the most abundant serum antibody and is an essential component of the humoral immune response. It is known that the 'neonatal' Fc receptor (FcRn) plays a role in maintaining constant serum IgG levels by acting as a protective receptor which binds and salvages IgG from degradation. However, the cellular mechanism that is involved in serum IgG homeostasis is poorly understood. In the current study we address this issue by analyzing the intracellular fate in human endothelial cells of IgG molecules which bind with different affinities to FcRn. The studies show that IgG which do not bind to FcRn accumulate in the lysosomal pathway, providing a cellular explanation for short serum persistence of such antibodies. We have also investigated the saturability of the homeostatic system and find that it has limited capacity. Our observations have direct relevance to the understanding and treatment of IgG deficiency, and to the effective application of therapeutic antibodies.