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

Shu Wang, Jingya Wang, Varsha Kumar, Jodi L. Karnell, Brian Naiman, Phillip S. Gross, Saifur Rahman, Kamelia Zerrouki, Richard Hanna, Christopher Morehouse, Nicholas Holoweckyj, Hao Liu, Zerai Manna, Raphaela Goldbach-Mansky, Sarfaraz Hasni, Richard Siegel, Miguel Sanjuan, Katie Streicher, Michael P. Cancro, Roland Kolbeck and Rachel Ettinger ()
Additional contact information
Shu Wang: MedImmune LLC
Jingya Wang: MedImmune LLC
Varsha Kumar: MedImmune LLC
Jodi L. Karnell: MedImmune LLC
Brian Naiman: MedImmune LLC
Phillip S. Gross: MedImmune LLC
Saifur Rahman: MedImmune LLC
Kamelia Zerrouki: MedImmune LLC
Richard Hanna: MedImmune LLC
Christopher Morehouse: MedImmune LLC
Nicholas Holoweckyj: MedImmune LLC
Hao Liu: MedImmune LLC
Zerai Manna: National Institutes of Health
Raphaela Goldbach-Mansky: National Institutes of Health
Sarfaraz Hasni: National Institutes of Health
Richard Siegel: National Institutes of Health
Miguel Sanjuan: MedImmune LLC
Katie Streicher: MedImmune LLC
Michael P. Cancro: University of Pennsylvania
Roland Kolbeck: MedImmune LLC
Rachel Ettinger: MedImmune LLC

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chiT-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 CD11chiT-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 CD11chiT-bet+ B cells in human SLE.

Date: 2018
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DOI: 10.1038/s41467-018-03750-7

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