Mincle and human B cell function

J Autoimmun. 2012 Dec;39(4):315-22. doi: 10.1016/j.jaut.2012.04.004. Epub 2012 Jun 12.

Abstract

C-type lectin receptors are pattern recognition receptors that are critical for autoimmunity and the immune response. Mincle is a C-type lectin receptor expressed by a variety of antigen presenting cells including macrophages, neutrophils, dendritic cells and B cells; a variety of stimuli including stress are known to induce the expression of Mincle. Mincle is an FcRγ-associated activation receptor that senses damaged cells and upon ligation induces activated macrophages to produce inflammatory cytokines. Recently, while several studies have reported that Mincle plays an important role in macrophage responses to fungal infection its function on B cells remains to be defined. In efforts to elucidate the function of Mincle expressed by B cells, we studied the expression of Mincle on subsets of B cells and analyzed cytokines and synthesized immunoglobulin upon ligation of Mincle. The expression of Mincle on CD27-CD19(+) naïve B cells is significantly higher than CD27 + CD19(+) memory B cells. The stimulation of TLR9 ligand induced Mincle expression on B cells. Furthermore, co-stimulation of TLR9 and Mincle ligand reduced IgG and IgA production from B cells without a significant change in the inflammatory cytokines TNF-α, IL-6, IL-8 and IL-10. Our data identifies Mincle as a potentially critical player in human B cell responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology*
  • Cells, Cultured
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • Glycolipids / pharmacology
  • Humans
  • Immunoglobulin A
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Immunologic Memory / drug effects
  • Immunologic Memory / immunology
  • Interleukin-10 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology*
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Oligodeoxyribonucleotides / pharmacology
  • Protein Binding
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antigens, CD19
  • CLEC4D protein, human
  • CpG-B 2006
  • Glycolipids
  • Immunoglobulin A
  • Immunoglobulin G
  • Interleukin-6
  • Interleukin-8
  • Lectins, C-Type
  • Lipopolysaccharides
  • Oligodeoxyribonucleotides
  • Receptors, Immunologic
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factor-alpha
  • trehalose 6,6'-dibehenate
  • Interleukin-10