| First Author | Hömig-Hölzel C | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 6 | Pages | 1317-29 |
| PubMed ID | 18490492 | Mgi Jnum | J:137122 |
| Mgi Id | MGI:3798033 | Doi | 10.1084/jem.20080238 |
| Citation | Homig-Holzel C, et al. (2008) Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-kappaB pathway and promotes lymphomagenesis. J Exp Med 205(6):1317-29 |
| abstractText | CD40, a member of the tumor necrosis factor (TNF) receptor family, plays an essential role in T cell-dependent 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-kappaB pathway and the mitogen-activated protein kinases Jnk and extracellular signal-regulated 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. |
