The success of Intravenous Immunoglobulin in treating autoimmune and inflammatory processes such as immune thrombocytopenia purpura and Kawasaki disease has led to renewed interest in developing recombinant molecules capable of recapitulating these therapeutic effects. The anti-inflammatory properties of IVIG are, in part, due to the Fc region of the IgG molecule, which interacts with activating or inhibitory Fcγ receptors (FcγRs), the neonatal Fc Receptor, non-canonical FcRs expressed by immune cells and complement proteins. In most cases, Fc interactions with these cognate receptors are dependent upon avidity—avidity which naturally occurs when polyclonal antibodies recognize unique antigens on a given target. The functional consequences of these avid interactions include antibody dependent cell-mediated cytotoxicity, antibody dependent cell phagocytosis, degranulation, direct killing, and/or complement activation—all of which are associated with long-term immunomodulatory effects. Many of these immunologic effects can be recapitulated using recombinant or non-recombinant approaches to induce Fc multimerization, affording the potential to develop a new class of therapeutics. In this review, we discuss the history of tolerance induction by immune complexes that has led to the therapeutic development of artificial Fc bearing immune aggregates and recombinant Fc multimers. The contribution of structure, aggregation and N-glycosylation to human IgG: FcγR interactions and the functional effect(s) of these interactions are reviewed. Understanding the mechanisms by which Fc multimers induce tolerance and attempts to engineer Fc multimers to target specific FcγRs and/or specific effector functions in autoimmune disorders is explored in detail.

静脉免疫球蛋白在治疗自身免疫和炎性过程（例如免疫性血小板减少性紫癜和川崎病）方面的成功，引起了人们对开发能够概括这些治疗作用的重组分子的新兴趣。IVIG的抗炎特性部分归因于IgG分子的Fc区，该区与激活或抑制性Fcγ受体（FcγRs），新生儿Fc受体，免疫细胞表达的非规范FcR和补体蛋白相互作用。在大多数情况下，与这些同源受体的Fc相互作用取决于亲和力-亲和力，当多克隆抗体识别给定靶标上的独特抗原时，自然发生。这些狂热相互作用的功能后果包括抗体依赖性细胞介导的细胞毒性，抗体依赖性细胞的吞噬作用，脱颗粒，直接杀伤和/或补体激活-所有这些都与长期免疫调节作用有关。可以使用重组或非重组方法诱导Fc多聚化来概括许多这些免疫学作用，从而提供开发新型治疗剂的潜力。在这篇综述中，我们讨论了免疫复合物诱导耐受的历史，该历史已导致具有人工Fc的免疫聚集体和重组Fc多聚体的治疗发展。审查了结构，聚集和N-糖基化对人IgG：FcγR相互作用的贡献以及这些相互作用的功能作用。