Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United States.
Department of Biosciences, University of Oslo, Oslo, Norway.
Front Immunol. 2019 Jul 10;10:1540. doi: 10.3389/fimmu.2019.01540. eCollection 2019.
Antibodies are essential components of an adaptive immune response. Immunoglobulin G (IgG) is the most common type of antibody found in circulation and extracellular fluids. Although IgG alone can directly protect the body from infection through the activities of its antigen binding region, the majority of IgG immune functions are mediated via proteins and receptors expressed by specialized cell subsets that bind to the fragment crystallizable (Fc) region of IgG. Fc gamma (γ) receptors (FcγR) belong to a broad family of proteins that presently include classical membrane-bound surface receptors as well as atypical intracellular receptors and cytoplasmic glycoproteins. Among the atypical FcγRs, the neonatal Fc receptor (FcRn) has increasingly gained notoriety given its intimate influence on IgG biology and its ability to also bind to albumin. FcRn functions as a recycling or transcytosis receptor that is responsible for maintaining IgG and albumin in the circulation, and bidirectionally transporting these two ligands across polarized cellular barriers. More recently, it has been appreciated that FcRn acts as an immune receptor by interacting with and facilitating antigen presentation of peptides derived from IgG immune complexes (IC). Here we review FcRn biology and focus on newer advances including how emerging FcRn-targeted therapies may affect the immune responses to IgG and IgG IC.
抗体是适应性免疫反应的重要组成部分。免疫球蛋白 G（IgG）是循环和细胞外液中最常见的抗体类型。虽然 IgG 本身可以通过其抗原结合区域的活性直接保护身体免受感染，但 IgG 的大多数免疫功能是通过与 IgG 的片段结晶区（Fc 区）结合的专门细胞亚群表达的蛋白质和受体来介导的。Fc 伽马（γ）受体（FcγR）属于一个广泛的蛋白质家族，目前包括经典的膜结合表面受体以及非典型的细胞内受体和细胞质糖蛋白。在非典型 FcγR 中，新生儿 Fc 受体（FcRn）因其对 IgG 生物学的密切影响及其与白蛋白结合的能力而越来越受到关注。FcRn 作为一种再循环或转胞吞作用受体，负责维持 IgG 和白蛋白在循环中的存在，并将这两种配体双向转运穿过极性细胞屏障。最近，人们认识到 FcRn 通过与 IgG 免疫复合物（IC）衍生的肽相互作用并促进其呈递而充当免疫受体。在这里，我们综述了 FcRn 的生物学，并重点介绍了新的进展，包括新兴的 FcRn 靶向治疗如何影响对 IgG 和 IgG IC 的免疫反应。
