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Scleroderma Peripheral B Lymphocytes Secrete Interleukin-6 and Transforming Growth Factor β and Activate Fibroblasts

Nicolas Dumoitier1, Benjamin Chaigne2, Alexis Régent2

  • 1INSERM U1016, Institut Cochin, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, LabEx Inflamex, Université Sorbonne Paris Cité and Université Paris Diderot, Paris, France.

Arthritis & Rheumatology (Hoboken, N.J.)
|December 20, 2016
PubMed

Insights

B lymphocytes in systemic sclerosis (SSc) patients show increased activation and secrete higher levels of IL-6 and TGFβ. These activated B cells promote fibroblast proliferation and collagen production, contributing to SSc pathogenesis.

Area of Science:

  • Immunology
  • Rheumatology
  • Cell Biology

Background:

  • Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis.
  • The role of B lymphocytes in SSc pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of B lymphocytes in systemic sclerosis (SSc).
  • To analyze B cell subpopulations and their cytokine production in SSc patients.

Main Methods:

  • Flow cytometry and multiplex assays were used to analyze peripheral B cell subpopulations and cytokine production (IL-6, TGFβ).
  • Fibroblast proliferation and collagen production were assessed in vitro using supernatants from SSc patient B cells.

Main Results:

  • SSc patients exhibited increased proportions of activated B cells (CD69+, CD95+).
  • B cells from SSc patients, particularly diffuse cutaneous SSc (dcSSc), showed higher expression of CD5, CD86, IL-6 receptor (IL-6R), and IL-21 receptor (IL-21R) compared to limited cutaneous SSc (lcSSc) and healthy controls.
  • B cells from SSc patients secreted significantly higher levels of IL-6 and TGFβ.
  • Supernatants from SSc B cells enhanced fibroblast proliferation and collagen production in vitro.

Conclusions:

  • Activated B cells are increased in SSc patients.
  • Specific markers on B cells (CD5, CD86, IL-6R, IL-21R) can differentiate between dcSSc and lcSSc subtypes.
  • Peripheral B lymphocytes in SSc patients contribute to disease pathology by secreting IL-6 and TGFβ, which activate fibroblasts.
Abstract

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