Immunoglobulin Y (IgY) is central to our understanding of immunoglobulin evolution. It has links to antibodies from the ancestral IgM to the mucosal IgX and IgA, as well as to mammalian serum IgG and IgE. IgY is found in amphibians, birds and reptiles, and as their most abundant serum antibody, is orthologous to mammalian IgG. However, IgY has the same domain architecture as IgM and IgE, lacking a hinge region and comprising four heavy‐chain constant domains. The relationship between IgY and the mucosal antibodies IgX and IgA is discussed herein, in particular the question of how IgA could have contributed to the emergence of IgY. Although IgY does not contain a hinge region, amphibian IgF and duck‐billed platypus IgY/O, which are closely related to IgY, do contain this region, as does mammalian IgG, IgA and IgD. A hinge region must therefore have evolved at least three times independently by convergent evolution. In the absence of three‐dimensional structural information for the complete Fc fragment of chicken IgY (IgY‐Fc), it remains to be discovered whether IgY displays the same conformational properties as IgM and IgE, which exhibit substantial flexibility in their Fc regions. IgY has three characterised Fc receptors, chicken Ig‐like receptor AB1 (CHIR‐AB1), the chicken yolk sac IgY receptor (FcRY) and Gallus gallus Fc receptor (ggFcR). These receptors bind to IgY at sites that are structurally homologous to mammalian counterparts; IgA/FcαRI for CHIR‐AB1, IgG/FcRn for FcRY and IgE/FcϵRI and IgG/FcγR for ggFcR. These resemblances reflect the close evolutionary relationships between IgY and IgA, IgG and IgE. However, the evolutionary distance between birds and mammals allows for the ready generation of IgY antibodies to conserved mammalian proteins for medical and biotechnological applications. Furthermore, the lack of reactivity of IgY with mammalian Fc receptors, and the fact that large quantities of IgY can be made quickly and cheaply in chicken eggs, offers important advantages and considerable potential for IgY in research, diagnostics and therapeutics.

中文翻译：

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IgY：抗体进化中的关键同种型

免疫球蛋白 Y (IgY) 是我们理解免疫球蛋白进化的核心。它与从祖先 IgM 到粘膜 IgX 和 IgA 以及哺乳动物血清 IgG 和 IgE 的抗体有关。IgY 存在于两栖动物、鸟类和爬行动物中，作为它们最丰富的血清抗体，与哺乳动物 IgG 直系同源。然而，IgY 具有与 IgM 和 IgE 相同的结构域结构，缺少铰链区并包含四个重链恒定结构域。本文讨论了 IgY 与黏膜抗体 IgX 和 IgA 之间的关系，特别是 IgA 如何促成 IgY 出现的问题。尽管 IgY 不包含铰链区，但与 IgY 密切相关的两栖动物 IgF 和鸭嘴兽 IgY/O 确实包含该区域，哺乳动物 IgG、IgA 和 IgD 也是如此。因此，铰链区必须通过趋同进化独立进化至少三次。在缺乏鸡 IgY 完整 Fc 片段 (IgY-Fc) 的三维结构信息的情况下，IgY 是否表现出与 IgM 和 IgE 相同的构象特性仍有待发现，IgM 和 IgE 在其 Fc 区域表现出很大的灵活性。IgY 具有三种特征 Fc 受体，鸡 Ig 样受体 AB1 (CHIR-AB1)、鸡卵黄囊 IgY 受体 (FcRY) 和鸡 Fc 受体 (ggFcR)。这些受体在结构上与哺乳动物对应物同源的位点与 IgY 结合；IgA/FcαRI 用于 CHIR-AB1，IgG/FcRn 用于 FcRY，IgE/FcεRI 和 IgG/FcγR 用于 ggFcR。这些相似性反映了 IgY 和 IgA、IgG 和 IgE 之间密切的进化关系。然而，鸟类和哺乳动物之间的进化距离使得针对保守哺乳动物蛋白质的 IgY 抗体可以随时生成，用于医学和生物技术应用。此外，IgY 缺乏与哺乳动物 Fc 受体的反应性，以及可以在鸡蛋中快速廉价地制备大量 IgY 的事实，为 IgY 在研究、诊断和治疗方面提供了重要的优势和巨大的潜力。