SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-11-3573. This Article Full Text (PDF) All Versions of this Article: 2002-11-3573v1 102/4/1374    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yazawa, N. Articles by Tamaki, K. Search for Related Content PubMed PubMed Citation Articles by Yazawa, N. Articles by Tamaki, K. Social Bookmarking                   What's this? Submitted November 26, 2002 Accepted April 3, 2003 CD19 regulates innate immunity by the toll-like receptor RP105 signaling in B lymphocytes Norihito Yazawa, Manabu Fujimoto*, Shinichi Sato, Kensuke Miyake, Noriko Asano, Yoshinori Nagai, Osamu Takeuchi, Kiyoshi Takeda, Hitoshi Okochi, Shizuo Akira, Thomas F Tedder, and Kunihiko Tamaki Department of Regenerative Medicine, Research Institute, International Medical Center of Japan, Tokyo, Japan Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan Department of Dermatology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan Division of Infectious Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Department of Immunology,, Duke University Medical Center, Durham, NC, USA * Corresponding author; email: mfujimoto{at}ri.imcj.go.jp. Lipopolysaccharide (LPS) is a major Gram-negative bacterial component that stimulates innate immune response and also induces B lymphocyte activation. Recent studies have revealed that common molecular patterns of microorganisms such as LPS are recognized by Toll-like receptors (TLRs). B cells have two known TLRs that mediate LPS signaling, TLR4 and RP105 (CD180). While TLR4 is expressed on immune cells of various types, RP105 is preferentially expressed on mature B cells. Here we demonstrate that CD19 plays a major role in regulating signal transduction through RP105. Anti-RP105 ligation induced normal proliferation of B cells from mice deficient for MyD88, an adaptor protein which mediates most TLR pathways. By contrast, the loss of CD19 resulted in modest B cell proliferation against anti-RP105 stimulation as well as LPS stimulation. LPS induced tyrosine phosphorylation of CD19, which was RP105-dependent but TLR4-independent. CD19 formed a complex with Lyn and Vav following RP105 ligation, and CD19 expression was required for optimal Lyn activation and Vav phosphorylation. Consistently, B cells deficient for CD19 exhibited specific defect in the activation of c-Jun N-terminal kinases following RP105 ligation and LPS stimulation. In contrast, CD19 and phosphatidylinositol 3-kinase independently regulated intracellular calcium mobilization induced by anti-RP105 stimulation. Thus, signaling through the B cell-specific LPS receptor RP105 is uniquely regulated by B cell-specific signaling component, Lyn/CD19/Vav complex. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Iwata, A. Yoshizaki, K. Komura, K. Shimizu, F. Ogawa, T. Hara, E. Muroi, S. Bae, M. Takenaka, T. Yukami, et al. CD19, a Response Regulator of B Lymphocytes, Regulates Wound Healing through Hyaluronan-Induced TLR4 Signaling Am. J. Pathol., August 1, 2009; 175(2): 649 - 660. [Abstract] [Full Text] [PDF] K. Yanaba, J.-D. Bouaziz, T. Matsushita, T. Tsubata, and T. F. Tedder The Development and Function of Regulatory B Cells Expressing IL-10 (B10 Cells) Requires Antigen Receptor Diversity and TLR Signals J. Immunol., June 15, 2009; 182(12): 7459 - 7472. [Abstract] [Full Text] [PDF] T. Kobayashi, K. Takahashi, Y. Nagai, T. Shibata, M. Otani, S. Izui, S. Akira, Y. Gotoh, H. Kiyono, and K. Miyake Tonic B cell activation by Radioprotective105/MD-1 promotes disease progression in MRL/lpr mice Int. Immunol., July 1, 2008; 20(7): 881 - 891. [Abstract] [Full Text] [PDF] A. Yoshizaki, Y. Iwata, K. Komura, F. Ogawa, T. Hara, E. Muroi, M. Takenaka, K. Shimizu, M. Hasegawa, M. Fujimoto, et al. CD19 Regulates Skin and Lung Fibrosis via Toll-Like Receptor Signaling in a Model of Bleomycin-Induced Scleroderma Am. J. Pathol., June 1, 2008; 172(6): 1650 - 1663. [Abstract] [Full Text] [PDF] C. M. Hammond, D. White, J. Tomic, Y. Shi, and D. E. Spaner Extracellular calcium sensing promotes human B-cell activation and function Blood, December 1, 2007; 110(12): 3985 - 3995. [Abstract] [Full Text] [PDF] S. Divanovic, A. Trompette, L. K. Petiniot, J. L. Allen, L. M. Flick, Y. Belkaid, R. Madan, J. J. Haky, and C. L. Karp Regulation of TLR4 signaling and the host interface with pathogens and danger: the role of RP105 J. Leukoc. Biol., August 1, 2007; 82(2): 265 - 271. [Abstract] [Full Text] [PDF] N. W. Kin and V. M. Sanders CD86 Regulates IgG1 Production via a CD19-Dependent Mechanism J. Immunol., August 1, 2007; 179(3): 1516 - 1523. [Abstract] [Full Text] [PDF] P. Lewkowicz, N. Lewkowicz, A. Sasiak, and H. Tchorzewski Lipopolysaccharide-Activated CD4+CD25+ T Regulatory Cells Inhibit Neutrophil Function and Promote Their Apoptosis and Death J. Immunol., November 15, 2006; 177(10): 7155 - 7163. [Abstract] [Full Text] [PDF] S. Divanovic, A. Trompette, S. F. Atabani, R. Madan, D. T. Golenbock, A. Visintin, R. W. Finberg, A. Tarakhovsky, S. N. Vogel, Y. Belkaid, et al. Inhibition of TLR-4/MD-2 signaling by RP105/MD-1 Innate Immunity, December 1, 2005; 11(6): 363 - 368. [Abstract] [PDF] M. Cohen-Sfady, G. Nussbaum, M. Pevsner-Fischer, F. Mor, P. Carmi, A. Zanin-Zhorov, O. Lider, and I. R. Cohen Heat Shock Protein 60 Activates B Cells via the TLR4-MyD88 Pathway J. Immunol., September 15, 2005; 175(6): 3594 - 3602. [Abstract] [Full Text] [PDF] C.-L. Chu and C. A. Lowell The Lyn Tyrosine Kinase Differentially Regulates Dendritic Cell Generation and Maturation J. Immunol., September 1, 2005; 175(5): 2880 - 2889. [Abstract] [Full Text] [PDF] S. Babu, C. P. Blauvelt, V. Kumaraswami, and T. B. Nutman Diminished Expression and Function of TLR in Lymphatic Filariasis: A Novel Mechanism of Immune Dysregulation J. Immunol., July 15, 2005; 175(2): 1170 - 1176. [Abstract] [Full Text] [PDF] B. Hebeis, E. Vigorito, D. Kovesdi, and M. Turner Vav proteins are required for B-lymphocyte responses to LPS Blood, July 15, 2005; 106(2): 635 - 640. [Abstract] [Full Text] [PDF] E. A. Hayashi, S. Akira, and A. Nobrega Role of TLR in B Cell Development: Signaling through TLR4 Promotes B Cell Maturation and Is Inhibited by TLR2 J. Immunol., June 1, 2005; 174(11): 6639 - 6647. [Abstract] [Full Text] [PDF] Y. Nagai, T. Kobayashi, Y. Motoi, K. Ishiguro, S. Akashi, S.-i. Saitoh, Y. Kusumoto, T. Kaisho, S. Akira, M. Matsumoto, et al. The Radioprotective 105/MD-1 Complex Links TLR2 and TLR4/MD-2 in Antibody Response to Microbial Membranes J. Immunol., June 1, 2005; 174(11): 7043 - 7049. [Abstract] [Full Text] [PDF] E. Diamant, Z. Keren, and D. Melamed CD19 regulates positive selection and maturation in B lymphopoiesis: lack of CD19 imposes developmental arrest of immature B cells and consequential stimulation of receptor editing Blood, April 15, 2005; 105(8): 3247 - 3254. [Abstract] [Full Text] [PDF] I. B. Bekeredjian-Ding, M. Wagner, V. Hornung, T. Giese, M. Schnurr, S. Endres, and G. Hartmann Plasmacytoid Dendritic Cells Control TLR7 Sensitivity of Naive B Cells via Type I IFN J. Immunol., April 1, 2005; 174(7): 4043 - 4050. [Abstract] [Full Text] [PDF] P. Li, T. Wohland, B. Ho, and J. L. Ding Perturbation of Lipopolysaccharide (LPS) Micelles by Sushi 3 (S3) Antimicrobial Peptide: THE IMPORTANCE OF AN INTERMOLECULAR DISULFIDE BOND IN S3 DIMER FOR BINDING, DISRUPTION, AND NEUTRALIZATION OF LPS J. Biol. Chem., November 26, 2004; 279(48): 50150 - 50156. [Abstract] [Full Text] [PDF] M. Yeh, N. M. Gharavi, J. Choi, X. Hsieh, E. Reed, K. P. Mouillesseaux, A. L. Cole, S. T. Reddy, and J. A. Berliner Oxidized Phospholipids Increase Interleukin 8 (IL-8) Synthesis by Activation of the c-src/Signal Transducers and Activators of Transcription (STAT)3 Pathway J. Biol. Chem., July 16, 2004; 279(29): 30175 - 30181. [Abstract] [Full Text] [PDF] J. W. Hollingsworth II, D. N. Cook, D. M. Brass, J. K. L. Walker, D. L. Morgan, W. M. Foster, and D. A. Schwartz The Role of Toll-like Receptor 4 in Environmental Airway Injury in Mice Am. J. Respir. Crit. Care Med., July 15, 2004; 170(2): 126 - 132. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020