Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
Department of Rheumatology and Immunology, First Hospital Affiliated to Baotou Medical College, Inner Mongolia Key Laboratory of Autoimmunity, Baotou, China.
Front Immunol. 2018 Mar 23;9:626. doi: 10.3389/fimmu.2018.00626. eCollection 2018.
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 CD19CD27IgD 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 CD27IgD 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 CD27IgD 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 CD27IgD B cells were impaired in RA with dysfunctional features, which might contribute to the disease perpetuation.
天然抗体，特别是天然 IgM，已被证明在抵御常见感染的免疫防御中发挥不可或缺的作用。最近，这些天然 IgM 的保护作用也在自身免疫性疾病中得到了认可。它们主要由 B-1 和先天样 B 细胞（ILB）产生。人类 CD19CD27IgD B 细胞，也称为未转换的记忆 B 细胞，被认为是一种 ILB。然而，这些细胞在类风湿关节炎（RA）中的功能特征和特性仍知之甚少。在这项研究中，我们发现人类 CD27IgD B 细胞可以产生天然抗体样 IgM。在 RA 情况下，这些细胞的频率明显降低。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，表现为多样性降低，并且 VH3-23D 向 VH1-8 的偏好性使用发生改变。单细胞测序进一步揭示了这些细胞在 RA 中的促炎偏向特征。这些 CD27IgD B 细胞与 RA 患者的疾病活动度和临床表现呈负相关。在 RA 患者经有效治疗达到疾病缓解后，这些细胞可以得到恢复。总之，这些结果表明，CD27IgD B 细胞在 RA 中受损，具有功能障碍特征，这可能导致疾病持续存在。
