Protein Interactions in Antibody Diversity

为了鉴定AID的抑制剂，NCATS在生物化学测定中对超过90，000种化合物进行了全面筛选。三种化合物显示出对鼠B细胞中重链类别转换的抑制。在生物测定中，化合物抑制AID而不是相关的APOBEC3蛋白。这些化合物可以被修饰以治疗由AID引起的疾病，例如B细胞淋巴瘤和自身免疫。关于自身免疫，我们已经确定了一个独特的B细胞群体，其标志是系统性红斑狼疮患者血液中CD 11 c表达升高。使用基因表达数据和IgH库分析，这个群体是不同于幼稚，记忆，或浆细胞。在类风湿性关节炎和慢性疟疾感染患者中发现了具有相似特征的细胞。这些细胞表达抑制B细胞受体信号传导的转录物，并在自身免疫过程中产生失调的抗体应答。

To identify inhibitors of AID, a comprehensive screen of over 90,000 compounds was performed by NCATS in biochemical assays. Three compounds showed inhibition of heavy chain class switching in murine B cells. The compounds inhibited AID and not a related APOBEC3 protein in a biological assay. These compounds may be modified to treat diseases caused by AID, such as B cell lymphomas and autoimmunity. Concerning autoimmunity, we have identified a distinct B cell population marked by elevated CD11c expression in the blood of patients with systemic lupus erythematosus. Using gene expression data and IgH repertoire analysis, this population was different than nave, memory, or plasma cells. Cells with similar characteristics were found in in patients with rheumatoid arthritis and chronic malarial infection. The cells express transcripts that dampen B cell receptor signaling and produce a dysregulated antibody response during autoimmunity.