Gessner J E, Heiken H, Tamm A, Schmidt R E
Department of Clinical Immunology, Hannover University Medical School, Germany.
Ann Hematol. 1998 Jun;76(6):231-48. doi: 10.1007/s002770050396.
IgG immune complexes are of central importance in the humoral immune system and strongly implicated in the pathogenesis of hematologic and rheumatic autoimmune disorders. Cross-linking of receptors for the Fc domain of IgG antibodies (FcgammaRs) triggers a wide variety of effector functions including phagocytosis, antibody-dependent cellular cytotoxicity, and release of inflammatory mediators, as well as immune complex clearance and regulation of antibody production. In this way, FcgammaR provide an essential feedback between the humoral and cellular immune response. In the past, significant advances have been made in the molecular dissection of FcgammaR function using cellular transfection systems. Current approaches designed to target and change individual FcgammaR genes in mice have given further insight into their specific contributions to systemic processes, also indicating them to be important immunoregulatory receptors involved in various disease states of allergy, autoimmunity, and inflammation. Future work on targeting FcgammaR binding sites in combination with humanized FcgammaR mouse models will lead to novel therapeutic strategies in the treatment of IgG-mediated human disease in which FcgammaR activation plays an integral part.
IgG免疫复合物在体液免疫系统中至关重要，并与血液学和风湿性自身免疫性疾病的发病机制密切相关。IgG抗体Fc结构域受体（FcγRs）的交联触发了多种效应功能，包括吞噬作用、抗体依赖性细胞毒性、炎症介质释放，以及免疫复合物清除和抗体产生的调节。通过这种方式，FcγRs在体液免疫和细胞免疫反应之间提供了重要的反馈。过去，利用细胞转染系统在FcγR功能的分子剖析方面取得了重大进展。目前旨在靶向和改变小鼠个体FcγR基因的方法，进一步深入了解了它们对全身过程的具体贡献，也表明它们是参与过敏、自身免疫和炎症等各种疾病状态的重要免疫调节受体。未来针对FcγR结合位点并结合人源化FcγR小鼠模型的研究，将为治疗FcγR激活起重要作用的IgG介导的人类疾病带来新的治疗策略。
