IGHV1-69 型类风湿因子常规识别模式的结构基础

Structural Basis of a Conventional Recognition Mode of IGHV1-69 Rheumatoid Factors.

机构信息

Department of Biological Science and Technology, Tokyo University of Science, Tokyo, Japan.

出版信息

Adv Exp Med Biol. 2021;21:171-182. doi: 10.1007/5584_2020_510.

DOI:10.1007/5584_2020_510

Abstract

Rheumatoid factors (RFs) are autoantibodies that recognize the fragment crystallizable (Fc) region of immunoglobulin G (IgG). Genetically diverse RFs are produced in rheumatoid arthritis patients; however, in hematologic diseases, such as cryoglobulinemia and B cell lymphoma, RFs from a limited combination of heavy chain V-region genes and J-region genes are produced in large quantities and forms immune complexes with IgG. These genetically limited RFs have historically been used for the immunochemical characterization of RFs. Among them, RFs derived from the heavy-chain germline gene IGHV1-69 are the most common. Recently, the crystal structure of an IGHV1-69-derived RF named YES8c was elucidated in complex with human IgG1-Fc. Based on the structure and mutant analyses, a recognition mechanism for the autoantigen (IgG-Fc) common to IGHV1-69-derived RFs was proposed. This review summarizes the immunochemical character of the IGHV1-69-derived RFs, and then focuses on the recognition mechanism of the IGHV1-69-derived RFs, referring the structural features of the IGHV1-69-derived neutralizing antibodies.

摘要

类风湿因子（RFs）是识别免疫球蛋白 G（IgG）片段结晶区（Fc）的自身抗体。在类风湿关节炎患者中产生了遗传上多样化的 RFs；然而，在血液疾病中，如冷球蛋白血症和 B 细胞淋巴瘤，大量产生了有限的重链 V 区基因和 J 区基因组合的 RFs，并与 IgG 形成免疫复合物。这些遗传上有限的 RFs 历来被用于 RF 的免疫化学表征。其中，源自重链胚系基因 IGHV1-69 的 RF 最为常见。最近，与人 IgG1-Fc 复合物的 IGHV1-69 衍生 RF 命名为 YES8c 的晶体结构得到了阐明。基于结构和突变分析，提出了一种针对 IGHV1-69 衍生 RF 共同的自身抗原（IgG-Fc）的识别机制。这篇综述总结了 IGHV1-69 衍生 RF 的免疫化学特征，然后重点介绍了 IGHV1-69 衍生 RF 的识别机制，并参考了 IGHV1-69 衍生中和抗体的结构特征。