| First Author | Stunz LL | Year | 2004 |
| Journal | Immunity | Volume | 21 |
| Issue | 2 | Pages | 255-66 |
| PubMed ID | 15308105 | Mgi Jnum | J:93594 |
| Mgi Id | MGI:3487196 | Doi | 10.1016/j.immuni.2004.07.008 |
| Citation | Stunz LL, et al. (2004) Expression of the cytoplasmic tail of LMP1 in mice induces hyperactivation of B lymphocytes and disordered lymphoid architecture. Immunity 21(2):255-66 |
| abstractText | The oncogenic EBV protein LMP1 mimics a dysregulated CD40 receptor in vitro. To compare CD40 and LMP1-mediated events in vivo, transgenic mice were engineered to express mouse CD40 (mCD40tg) or a protein with extracellular mCD40 and cytoplasmic LMP1 (mCD40-LMP1tg). Transgenic and CD40(-/-) mice were bred so that only the transgenic CD40 molecule is expressed in B cells, macrophages, and dendritic cells. mCD40-LMP1tg mice had normal lymphocyte subsets, and immunization elicited an antibody response featuring normal isotype switching, affinity maturation, and germinal center (GC) formation. However, unimmunized mCD40-LMP1tg mice had expanded immature and germinal center B cells, produced autoantibodies, exhibited marked splenomegaly and lymphadenopathy, and elevated serum IL-6. Thus, signaling through the LMP1 cytoplasmic tail results in amplified and abnormal mimicry of CD40 functions in vivo, indicating possible ways in which LMP1 contributes to the pathogenesis of EBV-associated human disease. |
