IL-21 drives expansion and plasma cell differentiation of autoreactive CD11c hi T-bet + B cells in SLE

Nat Commun. 2018 May 1;9(1):1758. doi: 10.1038/s41467-018-03750-7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocyte Subsets
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD11c Antigen / immunology*
  • Cell Differentiation / physiology*
  • Cohort Studies
  • Female
  • Humans
  • Interleukins / physiology*
  • Lupus Erythematosus, Systemic / metabolism*
  • Male
  • Middle Aged
  • Plasma Cells / cytology*
  • Plasma Cells / immunology
  • T-Box Domain Proteins / metabolism*
  • Young Adult

Substances

  • CD11c Antigen
  • Interleukins
  • T-Box Domain Proteins
  • interleukin-21