Human effector B lymphocytes express ARID3a and secrete interferon alpha

J Autoimmun. 2016 Dec:75:130-140. doi: 10.1016/j.jaut.2016.08.003. Epub 2016 Aug 10.

Abstract

Previously, we determined that enhanced disease activity in patients with systemic lupus erythematosus (SLE) was associated with dramatic increases in numbers of B lymphocytes expressing the transcription factor ARID3a. Our data now indicate ARID3a is important for interferon alpha (IFNa) expression and show a strong association between ARID3a expression and transcription of genes associated with lupus IFN signatures. Furthermore, both ARID3a and IFNa production were elicited in healthy control B cells upon stimulation with the TLR 9 agonist, CpG. Importantly, secretion of IFNa from ARID3a+ healthy B lymphocytes stimulated increased IFNa production in plasmacytoid dendritic cells. These data identify ARID3a+ B cells as a novel type of effector B cell, and link ARID3a expression in B lymphocytes to IFN-associated inflammatory responses in SLE.

Keywords: ARID3a; Effector B lymphocyte; Inflammation; Interferon alpha; Lupus.

MeSH terms

  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • DNA-Binding Proteins / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Gene Expression / drug effects
  • Gene Expression / immunology*
  • Humans
  • Interferon-alpha / blood
  • Interferon-alpha / immunology*
  • Interferon-alpha / metabolism
  • Oligodeoxyribonucleotides / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 9 / agonists
  • Toll-Like Receptor 9 / immunology
  • Toll-Like Receptor 9 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism

Substances

  • ARID3A protein, human
  • DNA-Binding Proteins
  • Interferon-alpha
  • Oligodeoxyribonucleotides
  • ProMune
  • Toll-Like Receptor 9
  • Transcription Factors