Impaired CD27(+)IgD(+) B Cells With Altered Gene Signature in Rheumatoid Arthritis.

Impaired CD27(+)IgD(+) B Cells With Altered Gene Signature in Rheumatoid Arthritis.
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类风湿关节炎中基因特征改变的 CD27( )IgD( ) B 细胞受损

DOI:
10.3389/fimmu.2018.00626
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发表时间:
2018
影响因子:
7.3
通讯作者:
Li Z
Li Z
中科院分区:
医学2区
文献类型:
--
作者:
Hu F;Zhang W;Shi L;Liu X;Jia Y;Xu L;Zhu H;Li Y;Xu D;Lu L;Qiu X;Liu W;Qiao J;Wang Y;Li Z

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天然抗体,特别是天然IgM,被证明在抵抗常见感染的免疫防御中起着不可或缺的作用。最近,这些天然IgM的保护作用也在自身免疫性疾病中被认识到。它们主要由B-1和先天性样B细胞(ILB)产生。人CD 19 + CD 27 +IgD+ B细胞,又称非转换记忆B细胞,被认为是一种ILB。然而,这些细胞在类风湿性关节炎(RA)的功能特点和特点仍然知之甚少。本研究发现人CD 27 +IgD+ B细胞可产生天然抗体样IgM。在RA环境下,这些细胞的频率显著降低。此外,这些细胞的IgM产生能力也受到抑制。有趣的是,这些细胞的BCR库在RA中发生了改变,表明从VH 3 - 23 D到VH 1 -8的优先使用改变降低了多样性。单细胞测序进一步揭示了RA中这些细胞的促炎偏向特征。这些CD 27 +IgD+ B细胞与RA患者的疾病活动和临床表现呈负相关。在RA疾病缓解的有效治疗后,这些细胞可以恢复。综上所述,这些结果表明,CD 27 +IgD+ B细胞受损的RA功能障碍的特点,这可能有助于疾病的延续。
Natural antibodies, particularly natural IgM, are proved to play indispensable roles in the immune defenses against common infections. More recently, the protective roles of these natural IgM were also recognized in autoimmune diseases. They are mainly produced by B-1 and innate-like B cells (ILBs). Human CD19+CD27+IgD+ B cells, also termed as un-switched memory B cells, were proposed to be a kind of ILBs. However, functional features and characteristics of these cells in rheumatoid arthritis (RA) remained poorly understood. In this study, we found that human CD27+IgD+ B cells could produce natural antibody-like IgM. Under RA circumstance, the frequencies of these cells were significantly decreased. Moreover, the IgM-producing capacities of these cells were also dampened. Interestingly, the BCR repertoire of these cells was altered in RA, demonstrating decreased diversity with preferential usage alteration from VH3-23D to VH1-8. Single cell sequencing further revealed the proinflammatory biased features of these cells in RA. These CD27+IgD+ B cells were negatively correlated with RA patient disease activities and clinical manifestations. After effective therapy with disease remission in RA, these cells could be recovered. Taken together, these results have revealed that CD27+IgD+ B cells were impaired in RA with dysfunctional features, which might contribute to the disease perpetuation.
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