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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-11-3569.
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Blood, 1 June 2003, Vol. 101, No. 11, pp. 4500-4504
IMMUNOBIOLOGY
A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells
Nadia L. Bernasconi,
Nobuyuki Onai, and
Antonio Lanzavecchia
From the Institute for Research in Biomedicine, Bellinzona, Switzerland.
Toll-like receptors (TLRs) are pattern recognition receptors that trigger innate immunity. In this study we investigated the expression of 10 TLRs in human naive and memory B-cell subsets. We report that in human naive B cells most TLRs are expressed at low to undetectable levels, but the expression of TLR9 and TLR10 is rapidly induced following B-cell-receptor (BCR) triggering. In contrast, memory B cells express several TLRs at constitutively high levels. The differential expression of TLR9 correlates with responsiveness to its agonist, CpG DNA. Thus, human memory B cells proliferate and differentiate to immunoglobulin (Ig)secreting cells in response to CpG, while naive B do so only if simultaneously triggered through the BCR. The BCR-induced expression of TLRs in human naive B cells prevents polyclonal activation in a primary response, because it restricts stimulation to antigen-specific B cells. In contrast, the constitutive expression of TLRs in memory B cells allows polyclonal activation of the entire memory pool. Thus, in human B cells TLRs are downstream of BCR and play a role both in the primary response and in the memory phase.

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Primary Allogeneic T-Cell Responses against Mantle Cell Lymphoma Antigen-Presenting Cells for Adoptive Immunotherapy after Stem Cell Transplantation
Clin. Cancer Res.,
July 15, 2005;
11(14):
5310 - 5318.
[Abstract]
[Full Text]
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J. Wang, R. Alvarez, G. Roderiquez, E. Guan, Q. Caldwell, J. Wang, M. Phelan, and M. A. Norcross
CpG-Independent Synergistic Induction of {beta}-Chemokines and a Dendritic Cell Phenotype by Orthophosphorothioate Oligodeoxynucleotides and Granulocyte-Macrophage Colony-Stimulating Factor in Elutriated Human Primary Monocytes
J. Immunol.,
May 15, 2005;
174(10):
6113 - 6121.
[Abstract]
[Full Text]
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G. Muehlinghaus, L. Cigliano, S. Huehn, A. Peddinghaus, H. Leyendeckers, A. E. Hauser, F. Hiepe, A. Radbruch, S. Arce, and R. A. Manz
Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells
Blood,
May 15, 2005;
105(10):
3965 - 3971.
[Abstract]
[Full Text]
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R. J. Bende, W. M. Aarts, R. G. Riedl, D. de Jong, S. T. Pals, and C. J.M. van Noesel
Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity
J. Exp. Med.,
April 18, 2005;
201(8):
1229 - 1241.
[Abstract]
[Full Text]
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B. Jahrsdorfer, L. Muhlenhoff, S. E. Blackwell, M. Wagner, H. Poeck, E. Hartmann, R. Jox, T. Giese, B. Emmerich, S. Endres, et al.
B-Cell Lymphomas Differ in their Responsiveness to CpG Oligodeoxynucleotides
Clin. Cancer Res.,
February 15, 2005;
11(4):
1490 - 1499.
[Abstract]
[Full Text]
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M. Odendahl, H. Mei, B. F. Hoyer, A. M. Jacobi, A. Hansen, G. Muehlinghaus, C. Berek, F. Hiepe, R. Manz, A. Radbruch, et al.
Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response
Blood,
February 15, 2005;
105(4):
1614 - 1621.
[Abstract]
[Full Text]
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P. Vanlandschoot, F. Van Houtte, P. Ulrichts, J. Tavernier, and G. Leroux-Roels
Immunostimulatory potential of hepatitis B nucleocapsid preparations: lipopolysaccharide contamination should not be overlooked
J. Gen. Virol.,
February 1, 2005;
86(2):
323 - 331.
[Abstract]
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K. B. Gorden, K. S. Gorski, S. J. Gibson, R. M. Kedl, W. C. Kieper, X. Qiu, M. A. Tomai, S. S. Alkan, and J. P. Vasilakos
Synthetic TLR Agonists Reveal Functional Differences between Human TLR7 and TLR8
J. Immunol.,
February 1, 2005;
174(3):
1259 - 1268.
[Abstract]
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K. U. Saikh, T. L. Kissner, A. Sultana, G. Ruthel, and R. G. Ulrich
Human Monocytes Infected with Yersinia pestis Express Cell Surface TLR9 and Differentiate into Dendritic Cells
J. Immunol.,
December 15, 2004;
173(12):
7426 - 7434.
[Abstract]
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A. Eaton-Bassiri, S. B. Dillon, M. Cunningham, M. A. Rycyzyn, J. Mills, R. T. Sarisky, and M. L. Mbow
Toll-Like Receptor 9 Can Be Expressed at the Cell Surface of Distinct Populations of Tonsils and Human Peripheral Blood Mononuclear Cells
Infect. Immun.,
December 1, 2004;
72(12):
7202 - 7211.
[Abstract]
[Full Text]
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F Y Liew, M Komai-Koma, and D Xu
A toll for T cell costimulation
Ann Rheum Dis,
November 1, 2004;
63(suppl_2):
ii76 - ii78.
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R. Lazarus, B. A. Raby, C. Lange, E. K. Silverman, D. J. Kwiatkowski, D. Vercelli, W. J. Klimecki, F. D. Martinez, and S. T. Weiss
TOLL-like Receptor 10 Genetic Variation Is Associated with Asthma in Two Independent Samples
Am. J. Respir. Crit. Care Med.,
September 15, 2004;
170(6):
594 - 600.
[Abstract]
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P. Lieby, V. Poindron, S. Roussi, C. Klein, A.-M. Knapp, J.-C. Garaud, M. Cerutti, T. Martin, and J.-L. Pasquali
Pathogenic antiphospholipid antibody: an antigen-selected needle in a haystack
Blood,
September 15, 2004;
104(6):
1711 - 1715.
[Abstract]
[Full Text]
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F. Takeshita, K. Suzuki, S. Sasaki, N. Ishii, D. M. Klinman, and K. J. Ishii
Transcriptional Regulation of the Human TLR9 Gene
J. Immunol.,
August 15, 2004;
173(4):
2552 - 2561.
[Abstract]
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C. Hausl, R. U. Ahmad, H. P. Schwarz, E. M. Muchitsch, P. L. Turecek, F. Dorner, and B. M. Reipert
Preventing restimulation of memory B cells in hemophilia A: a potential new strategy for the treatment of antibody-dependent immune disorders
Blood,
July 1, 2004;
104(1):
115 - 122.
[Abstract]
[Full Text]
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H. Poeck, M. Wagner, J. Battiany, S. Rothenfusser, D. Wellisch, V. Hornung, B. Jahrsdorfer, T. Giese, S. Endres, and G. Hartmann
Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help
Blood,
April 15, 2004;
103(8):
3058 - 3064.
[Abstract]
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H.-J. Anders, B. Banas, and D. Schlondorff
Signaling Danger: Toll-Like Receptors and their Potential Roles in Kidney Disease
J. Am. Soc. Nephrol.,
April 1, 2004;
15(4):
854 - 867.
[Abstract]
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M. Komai-Koma, L. Jones, G. S. Ogg, D. Xu, and F. Y. Liew
TLR2 is expressed on activated T cells as a costimulatory receptor
PNAS,
March 2, 2004;
101(9):
3029 - 3034.
[Abstract]
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B. J. Hebeis, K. Klenovsek, P. Rohwer, U. Ritter, A. Schneider, M. Mach, and T. H. Winkler
Activation of Virus-specific Memory B Cells in the Absence of T Cell Help
J. Exp. Med.,
February 17, 2004;
199(4):
593 - 602.
[Abstract]
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J. D. Marshall, E. M. Hessel, J. Gregorio, C. Abbate, P. Yee, M. Chu, G. V. Nest, R. L. Coffman, and K. L. Fearon
Novel chimeric immunomodulatory compounds containing short CpG oligodeoxyribonucleotides have differential activities in human cells
Nucleic Acids Res.,
September 1, 2003;
31(17):
5122 - 5133.
[Abstract]
[Full Text]
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