Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells

Stem Cells. 2015 Mar;33(3):880-91. doi: 10.1002/stem.1881.

Abstract

Mesenchymal or stromal stem cells (MSC) interact with cells of the immune system in multiple ways. Modulation of the immune system by MSC is believed to be a therapeutic option for autoimmune disease and transplant rejection. In recent years, B cells have moved into the focus of the attention as targets for the treatment of immune disorders. Current B-cell targeting treatment is based on the indiscriminate depletion of B cells. The aim of this study was to examine whether human adipose tissue-derived MSC (ASC) interact with B cells to affect their proliferation, differentiation, and immune function. ASC supported the survival of quiescent B cells predominantly via contact-dependent mechanisms. Coculture of B cells with activated T helper cells led to proliferation and differentiation of B cells into CD19(+) CD27(high) CD38(high) antibody-producing plasmablasts. ASC inhibited the proliferation of B cells and this effect was dependent on the presence of T cells. In contrast, ASC directly targeted B-cell differentiation, independently of T cells. In the presence of ASC, plasmablast formation was reduced and IL-10-producing CD19(+) CD24(high) CD38(high) B cells, known as regulatory B cells, were induced. These results demonstrate that ASC affect B cell biology in vitro, suggesting that they can be a tool for the modulation of the B-cell response in immune disease.

Keywords: B cell; Immunomodulation; Mesenchymal stem cell; Plasmablast; Regulatory B cell (Breg).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adipose Tissue / immunology
  • Apoptosis / immunology
  • B-Lymphocytes, Regulatory / cytology*
  • B-Lymphocytes, Regulatory / immunology
  • Cell Communication / immunology*
  • Cell Differentiation / immunology
  • Cell Growth Processes / immunology
  • Cell Survival / immunology
  • Coculture Techniques
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • Plasma Cells / cytology*
  • Plasma Cells / immunology
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology