Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Immunol. 2012 May 15;188(10):4741-5. doi: 10.4049/jimmunol.1102651. Epub 2012 Apr 9.
Fc receptor-like (FcRL) proteins are a family of cellular receptors homologous to FcγRI and are predominantly expressed by B cells. They function to costimulate or inhibit BCR signaling through consensus ITAMs and ITIMs; however, the extracellular ligands of these receptors remain unknown or controversial. In this study, we tested the ability of human FcRL proteins to bind Igs and found FcRL4 and FcRL5 to be bona fide Fc receptors. In cellular binding assays, FcRL4 bound efficiently to IgA and FcRL5 binds all IgG isotypes with varied efficiency. Additionally, we generated mAbs capable of specifically blocking these interactions. Given their expression on activated B cells and potential for inhibitory signaling, FcRL4 and FcRL5 are likely to be important for immune complex-dependent human B cell regulation, and they represent novel therapeutic targets for receptor blockade therapies.
Fc 受体样（FcRL）蛋白是一类与 FcγRI 同源的细胞受体，主要由 B 细胞表达。它们通过共识 ITAMs 和 ITIMs 来调节或抑制 BCR 信号转导；然而，这些受体的细胞外配体仍然未知或存在争议。在这项研究中，我们测试了人 FcRL 蛋白结合 Ig 的能力，发现 FcRL4 和 FcRL5 是真正的 Fc 受体。在细胞结合实验中，FcRL4 能够有效地结合 IgA，FcRL5 以不同的效率结合所有 IgG 同型。此外，我们还产生了能够特异性阻断这些相互作用的单克隆抗体。鉴于它们在活化 B 细胞上的表达和潜在的抑制信号转导能力，FcRL4 和 FcRL5 可能是免疫复合物依赖性人 B 细胞调节的重要因素，它们代表了受体阻断治疗的新的治疗靶点。
