BAFF augments IgA2 and IL-10 production by TLR7/8 stimulated total peripheral blood B cells

Eur J Immunol. 2018 Feb;48(2):283-292. doi: 10.1002/eji.201646861. Epub 2017 Oct 11.

Abstract

Class-switching of B cells to IgA can be induced via both T-cell-dependent and T-cell-independent mechanisms. IgA is most predominantly produced mucosally and is important for combating infections and allergies. In contrast to mice, humans have two forms of IgA; IgA1 and IgA2 with diverse tissue distribution. In early life, IgA levels might be sub-optimal especially during the fall season when bacterial and viral infections are more common. Therefore, we investigated using human B cells whether T-cell-independent factors -promoting cell survival, class switching and immunoglobulin secretion- BAFF, APRIL, IL-10 and retinoic acid can boost IgA production in the context of viral or bacterial infection. To this end total and naive peripheral blood B cells were stimulated with these factors for 6 days in the presence or absence of TLR7/8 agonist R848 (mimicking viral infection) or TLR9 agonist CpG-ODN (mimicking bacterial infection). We show that BAFF significantly augments IgA2 production in TLR7/8 stimulated mature, but not naïve B cells. In addition, BAFF augments IL-10 production and viability in TLR7/8 and TLR9 stimulated mature B cells. These data warrant further investigation of its role in immune regulation both in the periphery and mucosal tissues in early life or during disease.

Keywords: CD38; Class switch recombination; CpG-ODN; Plasma cell; Retinoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / metabolism*
  • B-Lymphocytes / physiology*
  • Blood Cells / immunology*
  • Cells, Cultured
  • Humans
  • Hypersensitivity / immunology*
  • Imidazoles / pharmacology
  • Immunoglobulin A / metabolism
  • Immunoglobulin Class Switching
  • Infections / immunology*
  • Interleukin-10 / metabolism
  • Lymphocyte Activation
  • Mice
  • Mucous Membrane / immunology*
  • Oligodeoxyribonucleotides / pharmacology
  • T-Lymphocytes / immunology*
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 8 / agonists
  • Toll-Like Receptor 8 / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism

Substances

  • B-Cell Activating Factor
  • Imidazoles
  • Immunoglobulin A
  • Oligodeoxyribonucleotides
  • TLR7 protein, human
  • TLR8 protein, human
  • TNFSF13B protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Interleukin-10
  • resiquimod