Mincle and human B cell function.
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.
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, 95616 CA, USA.
Kazuhito
K
Kawata
Petr
P
Illarionov
Guo-Xiang
GX
Yang
Thomas P
TP
Kenny
Weici
W
Zhang
Masanobu
M
Tsuda
Yugo
Y
Ando
Patrick S C
PS
Leung
Aftab A
AA
Ansari
M Eric
ME
Gershwin
D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006017:Glycolipids / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018941:Antigens, CD19; C482593:CLEC4D protein, human; C513201:CpG-B 2006; D006017:Glycolipids; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015850:Interleukin-6; D016209:Interleukin-8; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; C507803:trehalose 6,6'-dibehenate; D016753:Interleukin-10