Culton Donna A, Nicholas Matilda W, Bunch Donna O, Zhen Quan Li, Kepler Thomas B, Dooley Mary Anne, Mohan Chandra, Nachman Patrick H, Clarke Stephen H
Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
J Clin Immunol. 2007 Jan;27(1):53-68. doi: 10.1007/s10875-006-9051-1. Epub 2006 Dec 29.
: We report here that dysregulation of CD19, a coreceptor that augments B-cell receptor (BCR) signaling, occurs at two B-cell differentiative stages in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitis (SVV). The naïve B cells of nearly all SLE and ANCA-SVV patients express approximately 20% less CD19 than healthy control (HC) B cells. In contrast, a subset of memory B cells of some SLE and ANCA-SVV Pts (25-35%) express two to fourfold more CD19 than HC B cells. These CD19(hi) memory B cells are activated and exhibit evidence of antigen selection. Proteome array analysis of 67 autoantigens indicates that CD19(hi) SLE Pts exhibit a distinct autoantibody profile characterized by high levels of antibodies to small nuclear ribonucleoproteins and low levels of antiglomerular autoantibodies. These findings have implications for autoreactive B-cell activation and suggest a shared mechanism of B-cell tolerance loss in these two diseases.
我们在此报告，共受体CD19失调，其增强B细胞受体（BCR）信号传导，在系统性红斑狼疮（SLE）和抗中性粒细胞胞浆自身抗体（ANCA）相关小血管炎（SVV）患者的两个B细胞分化阶段出现。几乎所有SLE和ANCA - SVV患者的初始B细胞表达的CD19比健康对照（HC）B细胞少约20%。相反，一些SLE和ANCA - SVV患者的一部分记忆B细胞（25 - 35%）表达的CD19比HC B细胞多两到四倍。这些CD19高表达记忆B细胞被激活并表现出抗原选择的证据。对67种自身抗原的蛋白质组阵列分析表明，CD19高表达的SLE患者表现出独特的自身抗体谱，其特征是针对小核核糖核蛋白的抗体水平高，而抗肾小球自身抗体水平低。这些发现对自身反应性B细胞激活有影响，并提示这两种疾病中B细胞耐受性丧失的共同机制。
