| First Author | Pasqualucci L | Year | 2008 |
| Journal | Nat Genet | Volume | 40 |
| Issue | 1 | Pages | 108-12 |
| PubMed ID | 18066064 | Mgi Jnum | J:131307 |
| Mgi Id | MGI:3773479 | Doi | 10.1038/ng.2007.35 |
| Citation | Pasqualucci L, et al. (2008) AID is required for germinal center-derived lymphomagenesis. Nat Genet 40(1):108-12 |
| abstractText | Most human B cell non-Hodgkin's lymphomas (B-NHLs) derive from germinal centers (GCs), the structure in which B cells undergo somatic hypermutation (SHM) and class switch recombination (CSR) before being selected for high-affinity antibody production. The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant SHM, which arise from mistakes occurring during CSR and SHM. A direct link between these DNA remodeling events and GC lymphoma development, however, has not been demonstrated. Here we have crossed three mouse models of B cell lymphoma driven by oncogenes (Myc, Bcl6 and Myc/Bcl6; refs. 5,6) with mice lacking activation-induced cytidine deaminase (AID), the enzyme required for both CSR and SHM. We show that AID deficiency prevents Bcl6-dependent, GC-derived B-NHL, but has no impact on Myc-driven, pre-GC lymphomas. Accordingly, abrogation of AID is associated with the disappearance of CSR- and SHM-mediated structural alterations. These results show that AID is required for GC-derived lymphomagenesis, supporting the notion that errors in AID-mediated antigen-receptor gene modification processes are principal contributors to the pathogenesis of human B-NHL. |
