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

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 auto-reactive 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.