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The therapeutic implications of activated immune responses via the enigmatic immunoglobulin D
International Reviews of Immunology ( IF 4.3 ) Pub Date : 2021-01-07
Tue Gia Nguyen

Abstract

Immunoglobulin D (IgD) is an enigmatic antibody and the least appreciated member of the immunoglobulin (Ig) family. Since its discovery over half a century ago, the essence of its function in the immune system has been somewhat enigmatic and less well-defined than other antibody classes. Membrane-bound IgD (mIgD) is mostly recognized as B-cell receptor (BCR) while secreted IgD (sIgD) has been recently implicated in ‘arming’ basophils and mast cells in mucosal innate immunity. Activations of immune responses via mIgD-BCR or sIgD by specific antigens or anti-IgD antibody thereby produce a broad and complex mix of cellular, antibody and cytokine responses from both the innate and adaptive immune systems. Such broadly activated immune responses via IgD were initially deemed to potentiate and exacerbate the onset of autoimmune and allergic conditions. Paradoxically, treatments with anti-IgD antibody suppressed and ameliorated autoimmune conditions and allergic inflammations in mouse models without compromising the host’s general immune defence, demonstrating a unique and novel therapeutic application for anti-IgD antibody treatment. Herein, this review endeavored to collate and summarize the evidence of the unique characteristics and features of activated immune responses via mIgD-BCR and sIgD that revealed an unappreciated immune-regulatory function of IgD in the immune system via an amplifying loop of anti-inflammatory Th2 and tolerogenic responses, and highlighted a novel therapeutic paradigm in harnessing these immune responses to treat human autoimmune and allergic conditions.



中文翻译:

通过神秘的免疫球蛋白D激活的免疫反应的治疗意义

摘要

免疫球蛋白D(IgD)是一种神秘抗体,是免疫球蛋白(Ig)家族中最不被赞赏的成员。自半个多世纪以来被发现以来,其在免疫系统中功能的实质已比其他抗体类别有些难以捉摸,而且定义不清。膜结合型IgD(mIgD)通常被认为是B细胞受体(BCR),而分泌型IgD(sIgD)最近与黏膜先天免疫的“武装”嗜碱性粒细胞和肥大细胞有关。特异性抗原或抗IgD抗体通过mIgD-BCR或sIgD激活免疫应答,从而产生了先天和适应性免疫系统的细胞,抗体和细胞因子应答的广泛而复杂的混合物。最初认为这种通过IgD广泛激活的免疫反应可增强和加剧自身免疫和过敏性疾病的发作。矛盾的是,在小鼠模型中用抗IgD抗体进行的治疗抑制并改善了自身免疫状况和变态反应性炎症,而没有损害宿主的总体免疫防御能力,证明了抗IgD抗体治疗的独特而新颖的治疗应用。在此,本综述力图整理和总结通过mIgD-BCR和sIgD激活的免疫反应的独特特征的证据,该证据通过抗炎性Th2的放大环揭示了免疫系统中IgD的未调节的免疫调节功能。和耐受性应答,并强调了利用这些免疫应答来治疗人类自身免疫和过敏性疾病的新型治疗范例。用抗IgD抗体进行的治疗可以抑制和改善小鼠模型中的自身免疫状况和变态反应性炎症,而不会损害宿主的总体免疫防御能力,这证明了抗IgD抗体治疗的独特而新颖的治疗应用。在此,本综述力图整理和总结通过mIgD-BCR和sIgD激活的免疫反应的独特特征的证据,该证据通过抗炎性Th2的放大环揭示了免疫系统中IgD的未调节的免疫调节功能。和耐受性应答,并强调了利用这些免疫应答来治疗人类自身免疫和过敏性疾病的新型治疗范例。用抗IgD抗体进行的治疗可以抑制和改善小鼠模型中的自身免疫状况和变态反应性炎症,而不会损害宿主的总体免疫防御能力,这证明了抗IgD抗体治疗的独特而新颖的治疗应用。在此,本综述力图整理和总结通过mIgD-BCR和sIgD激活的免疫反应的独特特征的证据,该证据通过抗炎性Th2的放大环揭示了免疫系统中IgD的未调节的免疫调节功能。和耐受性应答,并强调了利用这些免疫应答来治疗人类自身免疫和过敏性疾病的新型治疗范例。展示了抗IgD抗体治疗的独特而新颖的治疗应用。在此,本综述力图整理和总结通过mIgD-BCR和sIgD激活的免疫反应的独特特征的证据,该证据通过抗炎性Th2的放大环揭示了免疫系统中IgD的未调节的免疫调节功能。和耐受性应答,并强调了利用这些免疫应答来治疗人类自身免疫和过敏性疾病的新型治疗范例。展示了抗IgD抗体治疗的独特而新颖的治疗应用。在此,本综述力图整理和总结通过mIgD-BCR和sIgD激活的免疫反应的独特特征的证据,该证据通过抗炎性Th2的放大环揭示了免疫系统中IgD的未调节的免疫调节功能。和耐受性应答,并强调了利用这些免疫应答来治疗人类自身免疫和过敏性疾病的新型治疗范例。

更新日期:2021-01-07
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