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B cells in rheumatoid arthritis synovial tissues encode focused antibody repertoires that include antibodies that stimulate macrophage TNF-α production.
Clinical Immunology ( IF 4.5 ) Pub Date : 2020-02-05 , DOI: 10.1016/j.clim.2020.108360
Serra E Elliott 1 , Sarah Kongpachith 1 , Nithya Lingampalli 1 , Julia Z Adamska 1 , Bryan J Cannon 1 , Lisa K Blum 1 , Michelle S Bloom 1 , Matthew Henkel 2 , Mandy J McGeachy 2 , Larry W Moreland 2 , William H Robinson 1
Affiliation  

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:

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。
更新日期:2020-02-06
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