Protein Interactions in Antibody Diversity

为了确定AID的抑制剂，NCATS在生化分析中对90,000多种化合物进行了全面筛选。3个化合物对小鼠B细胞重链类型转换有抑制作用。在生物测定中，这些化合物抑制AID，而不是相关的APOBEC3蛋白。这些化合物可能会被改造，以治疗由艾滋病引起的疾病，如B细胞淋巴瘤和自身免疫。关于自身免疫，我们已经确定了一种独特的B细胞群，其特征是系统性红斑狼疮患者血液中CD11c表达升高。根据基因表达数据和免疫球蛋白谱分析，这一群体不同于NAVE、Memory或浆细胞。在类风湿性关节炎和慢性疟疾感染患者体内也发现了具有相似特征的细胞。这些细胞表达的转录物会抑制B细胞受体信号，并在自身免疫过程中产生失调的抗体反应。

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.