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TLR1/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and memory B cell subsets to produce cytokines, chemokines, and hematopoietic growth factors.

Agrawal S, Gupta S - J. Clin. Immunol. (2010)

Bottom Line: However, GM-CSF and G-CSF production was predominantly induced by TLR2 agonist.Most cytokines/chemokines/hematopoietic growth factors were predominantly or exclusively produced by memory B cells, and in general, TLR2 signal was more powerful than signal provided viaTLR7 and TLR9.No significant secretion of eotaxin, IFN-α, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-7, IL-15, IL-17, IL-12p40, IL-12p70, and TNF-β (lymphotoxin) was observed.

View Article: PubMed Central - PubMed

Affiliation: Division of Basic and Clinical Immunology, Medical Sciences I, C-240, University of California, Irvine, CA 92697, USA. sagrawal@uci.edu

ABSTRACT
Recently, it has been reported that using multiple signals, murine and human B cells secrete several cytokines with pro-inflammatory and immunoregulatory properties. We present the first comprehensive analysis of 24 cytokines, chemokines, and hematopoietic growth factors production by purified human peripheral blood B cells (CD19+), and naive (CD19+CD27-) and memory (CD19+CD27+) B cells in response to direct and exclusive signaling provided by toll-like receptor (TLR) ligands Pam3CSK (TLR1/TLR2), Imiquimod (TLR7), and GpG-ODN2006 (TLR9). All three TLR ligands stimulated B cells (CD19+) to produce cytokines IL-1α, IL-1β, IL-6, TNF-α, IL-13, and IL-10, and chemokines MIP-1α, MIP-1β, MCP-1, IP-10, and IL-8. However, GM-CSF and G-CSF production was predominantly induced by TLR2 agonist. Most cytokines/chemokines/hematopoietic growth factors were predominantly or exclusively produced by memory B cells, and in general, TLR2 signal was more powerful than signal provided viaTLR7 and TLR9. No significant secretion of eotaxin, IFN-α, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-7, IL-15, IL-17, IL-12p40, IL-12p70, and TNF-β (lymphotoxin) was observed. These data demonstrate that human B cells can be directly activated viaTLR1/TLR2, TLR7, and TLR9 to induce secretion of cytokines, chemokines, and hematopoietic growth factors and suggest a role of B cells in immune response against microbial pathogenesis and immune homeostasis.

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TLR-induced production of hematopoietic growth factors by naive and memory B cells. Purified B cells were further separated into naive (CD27-) and memory (CD27+) B cells and stimulated with TLR ligands as described in Fig. 1. TLR1/TLR2 and TLR7 induced G-CSF and GM-CSF secretion almost exclusively by memory B cells. TLR9 stimulations did not induce secretion of either growth factor
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Fig7: TLR-induced production of hematopoietic growth factors by naive and memory B cells. Purified B cells were further separated into naive (CD27-) and memory (CD27+) B cells and stimulated with TLR ligands as described in Fig. 1. TLR1/TLR2 and TLR7 induced G-CSF and GM-CSF secretion almost exclusively by memory B cells. TLR9 stimulations did not induce secretion of either growth factor

Mentions: Both G-CSF and GM-CSF were predominantly produced by memory B cells upon signaling with Pam and ImQ. CpG failed to induce significant amounts of G-CSF and GM-CSF (Fig. 7).Fig. 7


TLR1/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and memory B cell subsets to produce cytokines, chemokines, and hematopoietic growth factors.

Agrawal S, Gupta S - J. Clin. Immunol. (2010)

TLR-induced production of hematopoietic growth factors by naive and memory B cells. Purified B cells were further separated into naive (CD27-) and memory (CD27+) B cells and stimulated with TLR ligands as described in Fig. 1. TLR1/TLR2 and TLR7 induced G-CSF and GM-CSF secretion almost exclusively by memory B cells. TLR9 stimulations did not induce secretion of either growth factor
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3064903&req=5

Fig7: TLR-induced production of hematopoietic growth factors by naive and memory B cells. Purified B cells were further separated into naive (CD27-) and memory (CD27+) B cells and stimulated with TLR ligands as described in Fig. 1. TLR1/TLR2 and TLR7 induced G-CSF and GM-CSF secretion almost exclusively by memory B cells. TLR9 stimulations did not induce secretion of either growth factor
Mentions: Both G-CSF and GM-CSF were predominantly produced by memory B cells upon signaling with Pam and ImQ. CpG failed to induce significant amounts of G-CSF and GM-CSF (Fig. 7).Fig. 7

Bottom Line: However, GM-CSF and G-CSF production was predominantly induced by TLR2 agonist.Most cytokines/chemokines/hematopoietic growth factors were predominantly or exclusively produced by memory B cells, and in general, TLR2 signal was more powerful than signal provided viaTLR7 and TLR9.No significant secretion of eotaxin, IFN-α, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-7, IL-15, IL-17, IL-12p40, IL-12p70, and TNF-β (lymphotoxin) was observed.

View Article: PubMed Central - PubMed

Affiliation: Division of Basic and Clinical Immunology, Medical Sciences I, C-240, University of California, Irvine, CA 92697, USA. sagrawal@uci.edu

ABSTRACT
Recently, it has been reported that using multiple signals, murine and human B cells secrete several cytokines with pro-inflammatory and immunoregulatory properties. We present the first comprehensive analysis of 24 cytokines, chemokines, and hematopoietic growth factors production by purified human peripheral blood B cells (CD19+), and naive (CD19+CD27-) and memory (CD19+CD27+) B cells in response to direct and exclusive signaling provided by toll-like receptor (TLR) ligands Pam3CSK (TLR1/TLR2), Imiquimod (TLR7), and GpG-ODN2006 (TLR9). All three TLR ligands stimulated B cells (CD19+) to produce cytokines IL-1α, IL-1β, IL-6, TNF-α, IL-13, and IL-10, and chemokines MIP-1α, MIP-1β, MCP-1, IP-10, and IL-8. However, GM-CSF and G-CSF production was predominantly induced by TLR2 agonist. Most cytokines/chemokines/hematopoietic growth factors were predominantly or exclusively produced by memory B cells, and in general, TLR2 signal was more powerful than signal provided viaTLR7 and TLR9. No significant secretion of eotaxin, IFN-α, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-7, IL-15, IL-17, IL-12p40, IL-12p70, and TNF-β (lymphotoxin) was observed. These data demonstrate that human B cells can be directly activated viaTLR1/TLR2, TLR7, and TLR9 to induce secretion of cytokines, chemokines, and hematopoietic growth factors and suggest a role of B cells in immune response against microbial pathogenesis and immune homeostasis.

Show MeSH
Related in: MedlinePlus