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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4595-4603. Prepublished online as a Blood First Edition Paper on December 12, 2008; DOI 10.1182/blood-2008-07-165456. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-165456v1 113/19/4595    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Zapata, J. M. Articles by Reed, J. C. Search for Related Content PubMed PubMed Citation Articles by Zapata, J. M. Articles by Reed, J. C. Related Collections Immunobiology Lymphoid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Lymphocyte-specific TRAF3 transgenic mice have enhanced humoral responses and develop plasmacytosis, autoimmunity, inflammation, and cancer Juan M. Zapata1,2, David Llobet1, Maryla Krajewska1, Sophie Lefebvre1, Christina L. Kress1, and John C. Reed1 1 Burnham Institute for Medical Research, La Jolla, CA; and 2 Centro de Biología Molecular Severo Ochoa, UAM/CSIC, Madrid, Spain Tumor necrosis factor (TNF) receptor–associated factor 3 (TRAF3) regulates both innate and adaptive immunity by modulating signaling by Toll-like receptors (TLR) and TNF receptors. TRAF3 was recently identified as a tumor suppressor in human multiple myeloma, suggesting a prominent role in plasma cell homeostasis. We have generated transgenic mice expressing human TRAF3 in lymphocytes. These mice are normal at birth, but they develop over time plasmacytosis and hypergammaglobulinemia, as well as systemic inflammation and tertiary lymphoid organ formation. The analysis of the humoral responses of the TRAF3 mice demonstrated increased responses to T-dependent and T-independent antigens with increased production of antigen-specific immunoglobulin Gs (IgGs) compared with wild-type mice. Furthermore, TLR-mediated IgG production is also increased in TRAF3 B cells. In addition, TRAF3 mice develop autoimmunity and are predisposed to cancer, particularly squamous cell carcinomas of the tongue ( 50% incidence) and salivary gland tumors. In summary, TRAF3 renders B cells hyperreactive to antigens and TLR agonists, promoting autoimmunity, inflammation, and cancer, hereby providing a new model for studying de novo carcinogenesis promoted by B cell–initiated chronic inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: TRAF3 in B cells: too much, too little, too bad P. Leif Bergsagel Blood 2009 113: 4481-4482. [Full Text] [PDF] This article has been cited by other articles: P. L. Bergsagel TRAF3 in B cells: too much, too little, too bad Blood, May 7, 2009; 113(19): 4481 - 4482. [Full Text] [PDF]

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