| First Author | Middendorp S | Year | 2009 |
| Journal | Blood | Volume | 114 |
| Issue | 11 | Pages | 2280-9 |
| PubMed ID | 19608748 | Mgi Jnum | J:152411 |
| Mgi Id | MGI:4358658 | Doi | 10.1182/blood-2009-03-208215 |
| Citation | Middendorp S, et al. (2009) Mice deficient for CD137 ligand are predisposed to develop germinal center-derived B-cell lymphoma. Blood 114(11):2280-9 |
| abstractText | In the germinal center (GC), B cells proliferate dramatically and diversify their immunoglobulin genes, which increases the risk of malignant transformation. The GC B-cell reaction relies on crosstalk with follicular dendritic cells (FDCs), to which the costimulatory receptor CD137 on FDCs and its ligand on GC B cells potentially contribute. We report that mice deficient for CD137 ligand (CD137L) are predisposed to develop B-cell lymphoma, with an incidence of approximately 60% at 12 months of age. Lymphoma membrane markers were characteristic of GC B cells. Longitudinal histologic analysis identified the GC as site of oncogenic transformation and classified 85% of the malignancies found in approximately 200 mice as GC-derived B-cell lymphoma. To delineate the mechanism underlying lymphomagenesis, gene expression profiles of wild-type and CD137L-deficient GC B cells were compared. CD137L deficiency was associated with enhanced expression of a limited gene set that included Bcl-10 and the GC response regulators Bcl-6, Spi-B, Elf-1, Bach2, and activation-induced cytidine deaminase. Among these are proto-oncogenes that mediate GC B-cell lymphoma development in humans. We conclude that CD137L ordinarily regulates the GC B-cell response and thereby acts as a tumor suppressor. |
