TLR9 responses of B cells are repressed by intravenous immunoglobulin through the recruitment of phosphatase

J Autoimmun. 2011 Nov;37(3):190-7. doi: 10.1016/j.jaut.2011.05.014.

Abstract

One way for intravenous Ig (IVIg) to affect responses of the B cells might be to operate through their TLR7 and TLR9. We confirm the ability of TLR agonists to induce CD25 expression in B cells. For this to occur, sialylated Fc-gamma of IgG included in the IVIg preparation are required. As a result, IVIg suppresses TLR-induced production of the proinflammatory IL-6, but not that of the anti-inflammatory IL-10. That is, IVIg mimics the effects of the MyD88 inhibitor. Finally, as we previously showed that IVIg induces CD22 to recruit the inhibitory SHP-1, we established that this enzyme was also involved in IVIg-induced inhibition of TLR9 signaling. This is the first report to demonstrate such a mechanism underlying the negative impact of IVIg on B lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cells, Cultured
  • Flow Cytometry
  • Humans
  • Immunoglobulins, Intravenous / pharmacology*
  • Interleukin-10 / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-6 / biosynthesis
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Molecular Sequence Data
  • Myeloid Differentiation Factor 88 / immunology
  • Myeloid Differentiation Factor 88 / metabolism
  • Oligodeoxyribonucleotides / pharmacology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialic Acid Binding Ig-like Lectin 2 / immunology
  • Sialic Acid Binding Ig-like Lectin 2 / metabolism
  • Signal Transduction / immunology*
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / immunology*
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 9 / agonists
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology*
  • Toll-Like Receptor 9 / metabolism

Substances

  • CD22 protein, human
  • IL2RA protein, human
  • Immunoglobulins, Intravenous
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-6
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Oligodeoxyribonucleotides
  • Sialic Acid Binding Ig-like Lectin 2
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Interleukin-10
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6