A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus

Madhvi Menon, Paul A Blair, David A Isenberg, Claudia Mauri

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Signals controlling the generation of regulatory B (Breg) cells remain ill-defined. Here we report an "auto"-regulatory feedback mechanism between plasmacytoid dendritic cells (pDCs) and Breg cells. In healthy individuals, pDCs drive the differentiation of CD19(+)CD24(hi)CD38(hi) (immature) B cells into IL-10-producing CD24(+)CD38(hi) Breg cells and plasmablasts, via the release of IFN-α and CD40 engagement. CD24(+)CD38(hi) Breg cells conversely restrained IFN-α production by pDCs via IL-10 release. In systemic lupus erythematosus (SLE), this cross-talk was compromised; pDCs promoted plasmablast differentiation but failed to induce Breg cells. This defect was recapitulated in healthy B cells upon exposure to a high concentration of IFN-α. Defective pDC-mediated expansion of CD24(+)CD38(hi) Breg cell numbers in SLE was associated with altered STAT1 and STAT3 activation. Both altered pDC-CD24(+)CD38(hi) Breg cell interactions and STAT1-STAT3 activation were normalized in SLE patients responding to rituximab. We propose that alteration in pDC-CD24(+)CD38(hi) Breg cell interaction contributes to the pathogenesis of SLE.

Original languageEnglish
Pages (from-to)683-697
Number of pages15
Issue number3
Publication statusPublished - 15 Mar 2016


  • Adult
  • Aged
  • Antigens, CD/metabolism
  • Antirheumatic Agents/administration & dosage
  • B-Lymphocytes, Regulatory/drug effects
  • Cell Communication/drug effects
  • Cell Differentiation/drug effects
  • Cells, Cultured
  • Dendritic Cells/drug effects
  • Female
  • Homeostasis/drug effects
  • Humans
  • Interferon-gamma/metabolism
  • Interleukin-10/metabolism
  • Lupus Erythematosus, Systemic/drug therapy
  • Male
  • Middle Aged
  • Rituximab/administration & dosage
  • STAT1 Transcription Factor/metabolism
  • STAT3 Transcription Factor/metabolism
  • Transcriptional Activation/drug effects
  • Young Adult


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