IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE

作者：Shu Wang, Jingya Wang, Varsha Vimal Kumar, Jodi L. Karnell, Brian M. Naiman, Phillip S. Gross, Saifur Rahman, Kamelia Zerrouki, Richard N. Hanna, Christopher A. Morehouse, Nicholas Holoweckyj, Hao Liu, Autoimmunity Molecular Medicine Team, Kerry Anne Casey, Michael A. Smith, Melissa Parker, Natalie White, Jeffrey M. Riggs, Beth K. Ward, Geetha Bhat, Bhargavi Rajan, R W Grady, Chris Groves, Zerai G. Manna, Raphaela T. Goldbach‐Mansky, Sarfaraz Hasni, Richard M. Siegel, Miguel A. F. Sanjuán, Katie L. Streicher, Michael P. Cancro, Roland Kolbeck, Rachel Ettinger · 发表于：Nature Communications · 年份：2018 · DOI：10.1038/s41467-018-03750-7 · 被引用次数：601 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Chronic Lymphocytic Leukemia Research

Abstract Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11c hi T-bet + B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. IL-21 can potently induce CD11c hi T-bet + B cells and promote the differentiation of these cells into Ig-secreting autoreactive plasma cells. While murine studies have identified a role for T-bet-expressing B cells in autoimmunity, this study describes and exemplifies the importance of CD11c hi T-bet + B cells in human SLE.