IL-21 drives expansion and plasma cell differentiation of autoreactive CD11cT-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, Autoimmunity Molecular Medicine Team, Zerai Manna, Raphaela Goldbach-Mansky, Sarfaraz Hasni, Richard Siegel, Miguel Sanjuan, Katie Streicher, Michael P Cancro, Roland Kolbeck, Rachel Ettinger
Author Information
Shu Wang: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Jingya Wang: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Varsha Kumar: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Jodi L Karnell: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Brian Naiman: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Phillip S Gross: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA. ORCID
Saifur Rahman: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Kamelia Zerrouki: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Richard Hanna: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Christopher Morehouse: Translational Medicine, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Nicholas Holoweckyj: Translational Medicine, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Hao Liu: Translational Medicine, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Zerai Manna: The Office of Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Raphaela Goldbach-Mansky: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Sarfaraz Hasni: The Office of Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. ORCID
Richard Siegel: The Office of Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Miguel Sanjuan: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Katie Streicher: Translational Medicine, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Michael P Cancro: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Roland Kolbeck: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA.
Rachel Ettinger: Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD, 20878, USA. ettingerr@vielabio.com. ORCID
Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11cT-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 CD11cT-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 CD11cT-bet B cells in human SLE.
