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

著者: Shu Wang, Jingya Wang, Varsha Kumar, Jodi L. Karnell, Brian Naiman, Phillip S. Gross, Saifur Rahman, Kamelia Zerrouki, Richard N. Hanna, Christopher Morehouse, Nicholas Holoweckyj, Hao Liu, Autoimmunity Molecular Medicine Team, Kerry A. Casey, Michael A. Smith, Melissa Parker, Natalie White, Jeffrey M. Riggs, Beth K. Ward, Geetha Bhat, Bhargavi Rajan, R W Grady, Chris Groves, Zerai Manna, Raphaela Goldbach‐Mansky, Sarfaraz Hasni, Richard M. Siegel, Miguel A. F. Sanjuán, Katie Streicher, Michael P. Cancro, Roland Kolbeck, Rachel Ettinger - Nature Communications 2018 被引用: 569

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.