Rheumatoid arthritis (RA) is characterized by the production of anti-citrullinated protein antibodies (ACPAs). To gain insights into the relationship between ACPA-expressing B cells in peripheral blood (PB) and synovial tissue (ST), we sequenced the B cell repertoire in paired PB and ST samples from five individuals with established, ACPA+ RA. Bioinformatics analysis of paired heavy- and light-chain sequences revealed clonally-related family members shared between PB and ST. ST-derived antibody repertoires exhibited reduced diversity and increased normalized clonal family size compared to PB-derived repertoires. Functional characterization showed that seven recombinant antibodies (rAbs) expressed from subject-derived sequences from both compartments bound citrullinated antigens and immune complexes (ICs) formed using one ST-derived rAb stimulated macrophage TNF-α production. Our findings demonstrate B cell trafficking between PB and ST in subjects with RA and ST repertoires include B cells that encode ACPA capable of forming ICs that stimulate cellular responses implicated in RA pathogenesis.

中文翻译：

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类风湿关节炎滑膜组织中的B细胞编码集中的抗体库，其中包括刺激巨噬细胞TNF-α产生的抗体。

类风湿关节炎（RA）的特征是产生抗瓜氨酸化蛋白抗体（ACPA）。为了深入了解外周血中表达ACPA的B细胞（PB）和滑膜组织（ST）之间的关系，我们对来自已建立ACPA + RA的五个个体的成对PB和ST样本中的B细胞库进行了测序。对重链和轻链序列进行的生物信息学分析显示，PB和ST之间存在克隆相关的家族成员。与PB衍生的库相比，ST衍生的抗体库显示出降低的多样性并增加了标准化的克隆家族大小。功能表征表明，从两个区室的受试者衍生序列表达的七种重组抗体（rAb）结合瓜氨酸化抗原和使用一种ST衍生rAb刺激巨噬细胞TNF-α生成的免疫复合物（IC）。我们的发现表明，患有RA和ST的受试者中PB和ST之间的B细胞转运，包括编码ACPA的B细胞，能够形成能够刺激IC刺激与RA发病机制有关的IC的ACPA。