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.
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.
Agrawal
Sudhanshu
S
Division of Basic and Clinical Immunology, Medical Sciences I, C-240, University of California, Irvine, CA 92697, USA. sagrawal@uci.edu
Gupta
Sudhir
S
D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D006410:Hematopoiesis; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008024:Ligands; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000276:immunology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; C495342:TLR2 protein, human; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
Eur J Immunol. 2007 Dec;37(12):3304-10
18000957
Annu Rev Immunol. 2003;21:335-76
12524386
J Biol Chem. 1995 Nov 10;270(45):27348-57
7592998
Immunity. 2010 Jan 29;32(1):129-40
20079667
J Immunol. 2007 Mar 1;178(5):2803-12
17312124
Nat Rev Rheumatol. 2009 Oct;5(10):554-9
19798030
Structure. 2010 Mar 10;18(3):332-42
20223216
Cell Immunol. 2005 Jul-Aug;236(1-2):140-5
16188245
J Clin Immunol. 2005 Jan;25(1):29-40
15742155
Eur J Immunol. 2007 Aug;37(8):2205-13
17621369
J Exp Med. 2007 May 14;204(5):1107-18
17485512
J Exp Med. 1999 Jan 4;189(1):1-12
9874559
J Immunol. 2005 Apr 1;174(7):4043-50
15778362
J Immunol. 2004 Jan 15;172(2):954-63
14707068
Immunol Today. 1997 Jul;18(7):343-50
9238838
Autoimmun Rev. 2009 Mar;8(5):379-83
19105984
Immunology. 2006 Aug;118(4):539-48
16780564
Immunology. 2008 Nov;125(3):430-7
18445007
J Immunol. 2007 May 15;178(10):6092-9
17475834
Eur J Immunol. 2006 Apr;36(4):810-6
16541472
J Leukoc Biol. 2009 Aug;86(2):261-71
19401392
Immunology. 2006 May;118(1):66-77
16630024
J Immunol. 2002 May 1;168(9):4531-7
11970999
Mucosal Immunol. 2009 May;2(3):265-75
19262501
J Immunol. 2005 May 15;174(10):6308-13
15879130
Nat Rev Immunol. 2008 May;8(5):391-7
18437156
Adv Exp Med Biol. 2005;560:11-8
15932016
Eur J Immunol. 2007 Nov;37(11):3040-53
17918201
Curr Opin Immunol. 2008 Jun;20(3):332-8
18417336
J Exp Med. 1987 Oct 1;166(4):1084-97
2443596
J Immunol. 2006 Jan 15;176(2):705-10
16393950
BMC Immunol. 2008 Jul 24;9:39
18652679
Nature. 1995 Apr 6;374(6522):546-9
7700380
Cytokine Growth Factor Rev. 2002 Dec;13(6):455-81
12401480
Semin Immunol. 2007 Feb;19(1):24-32
17275323
Adv Immunol. 2008;98:1-38
18772002