IL-10-overexpressing B cells regulate innate and adaptive immune responses

J Allergy Clin Immunol. 2015 Mar;135(3):771-80.e8. doi: 10.1016/j.jaci.2014.07.041. Epub 2014 Sep 18.


Background: Distinct human IL-10-producing B-cell subsets with immunoregulatory properties have been described. However, the broader spectrum of their direct cellular targets and suppressive mechanisms has not been extensively studied, particularly in relation to direct and indirect IL-10-mediated functions.

Objective: The aim of the study was to investigate the effects of IL-10 overexpression on the phenotype and immunoregulatory capacity of B cells.

Methods: Primary human B cells were transfected with hIL-10, and IL-10-overexpressing B cells were characterized for cytokine and immunoglobulin production by means of specific ELISA and bead-based assays. Antigen presentation, costimulation capacity, and transcription factor signatures were analyzed by means of flow cytometry and quantitative RT-PCR. Effects of IL-10-overexpresing B cells on Toll-like receptor-triggered cytokine release from PBMCs, LPS-triggered maturation of monocyte-derived dendritic cells, and tetanus toxoid-induced PBMC proliferation were assessed in autologous cocultures.

Results: IL-10-overexpressing B cells acquired a prominent immunoregulatory profile comprising upregulation of suppressor of cytokine signaling 3 (SOCS3), glycoprotein A repetitions predominant (GARP), the IL-2 receptor α chain (CD25), and programmed cell death 1 ligand 1 (PD-L1). Concurrently, their secretion profile was characterized by a significant reduction in levels of proinflammatory cytokines (TNF-α, IL-8, and macrophage inflammatory protein 1α) and augmented production of anti-inflammatory IL-1 receptor antagonist and vascular endothelial growth factor. Furthermore, IL-10 overexpression was associated with a decrease in costimulatory potential. IL-10-overexpressing B cells secreted less IgE and potently suppressed proinflammatory cytokines in PBMCs, maturation of monocyte-derived dendritic cells (rendering their profile to regulatory phenotype), and antigen-specific proliferation in vitro.

Conclusion: Our data demonstrate an essential role for IL-10 in inducing an immunoregulatory phenotype in B cells that exerts substantial anti-inflammatory and immunosuppressive functions.

Keywords: IL-10 overexpression; anti-inflammatory effects; immune regulation; immunoregulatory capacity; regulatory B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology
  • Cell Differentiation
  • Cell Proliferation
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / immunology
  • Coculture Techniques
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate*
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Lipopolysaccharides / pharmacology
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Primary Cell Culture
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / immunology
  • Signal Transduction
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Tetanus Toxoid / pharmacology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / immunology


  • B7-H1 Antigen
  • CD274 protein, human
  • CXCL8 protein, human
  • Chemokine CCL3
  • IL10 protein, human
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-8
  • LRRC32 protein, human
  • Lipopolysaccharides
  • Membrane Proteins
  • Receptors, Interleukin-1
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Tetanus Toxoid
  • Tumor Necrosis Factor-alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Interleukin-10