B-cell activating factor (BAFF) promotes CpG ODN-induced B cell activation and proliferation

Cell Immunol. 2011;271(1):16-28. doi: 10.1016/j.cellimm.2011.05.016. Epub 2011 Jun 14.

Abstract

It is controversial whether naïve B cells are directly activated in response to TLR9 ligand, CpG ODN. Although bovine blood-derived CD21(+) B cells express TLR9 and proliferate in response to CpG in mixed-cell populations, purified bovine B cells do not proliferate significantly in response to CpG ODN, even when the B cell receptor is engaged. When co-cultured with CD14(+) myeloid cells and/or B-cell activating factor (BAFF), a cytokine produced by activated myeloid cells, there was a significant increase in CpG-specific B cell proliferation, and the number of large B cells in general or positive for CD25, all of which are markers for B cell activation. These data suggest that activated myeloid cells and BAFF prime B cells for significant CpG-specific activation. Understanding the signals required to mediate efficient CpG-induced, antigen-independent and T-cell independent activation of B cells has implications for polyclonal B cell activation and the development of autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / immunology
  • B-Cell Activating Factor / pharmacology*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cattle
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Coculture Techniques
  • Drug Synergism
  • Flow Cytometry
  • HEK293 Cells
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharide Receptors / immunology
  • Lipopolysaccharide Receptors / metabolism
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Male
  • Myeloid Cells / drug effects
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Oligodeoxyribonucleotides / pharmacology*
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Complement 3d / immunology
  • Receptors, Complement 3d / metabolism
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology
  • Toll-Like Receptor 9 / metabolism

Substances

  • B-Cell Activating Factor
  • CPG-oligonucleotide
  • Lipopolysaccharide Receptors
  • Oligodeoxyribonucleotides
  • Receptors, Antigen, B-Cell
  • Receptors, Complement 3d
  • Recombinant Proteins
  • Toll-Like Receptor 9