{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:23:00Z","timestamp":1791397380769,"version":"4.3.3"},"reference-count":48,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,6,9]]},"abstract":"<jats:p>CD40, a member of the tumor necrosis factor (TNF) receptor family, plays an essential role in T cell\u2013dependent immune responses. Because CD40 is widely expressed on the surface of tumor cells in various B cell malignancies, deregulated CD40 signaling has been suggested to contribute to lymphomagenesis. In this study, we show that B cell-specific expression of a constitutively active CD40 receptor, in the form of a latent membrane protein 1 (LMP1)\/CD40 chimeric protein, promoted an increase in the number of follicular and marginal zone B cells in secondary lymphoid organs in transgenic mice. The B cells displayed an activated phenotype, prolonged survival and increased proliferation, but were significantly impaired in T cell-dependent immune responses. Constitutive CD40 signaling in B cells induced selective and constitutive activation of the noncanonical NF-\u03baB pathway and the mitogen-activated protein kinases Jnk and extracellular signal\u2013regulated kinase. LMP1\/CD40-expressing mice older than 12 mo developed B cell lymphomas of mono- or oligoclonal origin at high incidence, thus showing that the interplay of the signaling pathways induced by constitutive CD40 signaling is sufficient to initiate a tumorigenic process, ultimately leading to the development of B cell lymphomas.<\/jats:p>","DOI":"10.1084\/jem.20080238","type":"journal-article","created":{"date-parts":[[2008,5,20]],"date-time":"2008-05-20T13:34:02Z","timestamp":1211290442000},"page":"1317-1329","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":122,"title":["Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-\u03baB pathway and promotes lymphomagenesis"],"prefix":"10.1084","volume":"205","author":[{"given":"Cornelia","family":"Ho\u0308mig-Ho\u0308lzel","sequence":"first","affiliation":[{"name":"1Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Center Munich, German Research Center for Environment and Health, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Hojer","sequence":"additional","affiliation":[{"name":"1Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Center Munich, German Research Center for Environment and Health, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Rastelli","sequence":"additional","affiliation":[{"name":"1Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Center Munich, German Research Center for Environment and Health, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Casola","sequence":"additional","affiliation":[{"name":"2Immune Disease Institute, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar J.","family":"Strobl","sequence":"additional","affiliation":[{"name":"1Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Center Munich, German Research Center for Environment and Health, D-81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Mu\u0308ller","sequence":"additional","affiliation":[{"name":"3The Department of Experimental Immunology, Helmholtz Center for Infectious Research, D-38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Quintanilla-Martinez","sequence":"additional","affiliation":[{"name":"4Institute of Pathology, Helmholtz Center Munich, German Research Center for Environment and Health, D-85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Gewies","sequence":"additional","affiliation":[{"name":"5III Med. 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