Coriolus versicolor mushroom polysaccharides exert immunoregulatory effects on mouse B cells via membrane Ig and TLR-4 to activate the MAPK and NF-κB signaling pathways

Mol Immunol. 2015 Mar;64(1):144-51. doi: 10.1016/j.molimm.2014.11.007. Epub 2014 Dec 3.

Abstract

This study aimed to characterize the immunopotentiating effects and immune receptors for Coriolus versicolor mushroom polysaccharides (CVP), a Chinese medicinal fungus that exerts anti-tumor activities by enhancing host immunity. Proliferation assays were used to determine whether CVP could activate splenocytes. Flow cytometry analysis and IgM and IgG detection were used to characterize CVP-binding cells. Immune receptors were analyzed in immunoprecipitation and western blot assays. The downstream signaling pathways were identified by western blotting or immunostaining. CVP significantly stimulated the proliferation of mouse splenocytes. Fluorescence-labeled CVP (fl-CVP) selectively stained mouse B cells, but not T cells. CVP induced the production of IgM and IgG1 with or without exogenous IL-4. Membrane Ig (B cell antigen-receptor, BCR) was identified as a CVP-binding protein in immunoprecipitation and western blot experiments. CVP-induced B cell proliferation could be significantly inhibited by anti-mouse immunoglobulin (Ig) blocking antibody (Fab) or in cells from TLR4-mutant mice (C3H/HeJ). Phosphorylation of ERK-1/2 and p38 MAPK were clearly increased in a time-dependent manner, as was the nuclear translocation of the cytosolic NF-κB p65 subunit after CVP stimulation. Together, we demonstrate that CVP can bind and induce B cell activation using membrane Ig and TLR-4 as potential immune receptors. CVP activates mouse B cells through the MAPK and NF-κB signaling pathways.

Keywords: B cell antigen-receptor (BCR); Coriolus versicolor mushroom polysaccharides (CVP); Immunopotentiating effects; Leukocytes; TLR-4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / chemistry*
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Proliferation / drug effects
  • Chromatography, High Pressure Liquid
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Fluorescence
  • Immunoglobulin Class Switching / drug effects
  • Immunoglobulins / metabolism*
  • Immunomodulation / drug effects*
  • Interleukin-2 / biosynthesis
  • Kinetics
  • Lymphocyte Activation / drug effects
  • Mice, Inbred BALB C
  • Monocytes / drug effects
  • Monocytes / metabolism
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Polysaccharides / pharmacology*
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction / drug effects*
  • Spleen / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 4 / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Immunoglobulins
  • Interleukin-2
  • NF-kappa B
  • Polysaccharides
  • Receptors, Antigen, B-Cell
  • Toll-Like Receptor 4
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases