Protein Interactions in Antibody Diversity

点击翻译按钮获取中文摘要

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.