| First Author | Roundy KM | Year | 2005 |
| Journal | Int Immunol | Volume | 17 |
| Issue | 11 | Pages | 1495-503 |
| PubMed ID | 16186160 | Mgi Jnum | J:102222 |
| Mgi Id | MGI:3607071 | Doi | 10.1093/intimm/dxh327 |
| Citation | Roundy KM, et al. (2005) Partial rescue of B cells in microphthalmic osteopetrotic marrow by loss of response to type I IFNs. Int Immunol 17(11):1495-503 |
| abstractText | The microphthalmic (mi) mouse exhibits deficiencies in the development of osteoclasts, melanocytes, mast cells and marrow B cells. Previously, we demonstrated that the marrow of such mice over-express receptor activator of nuclear factor kappaB (RANK) ligand (RANKL). RANKL has been shown to induce the production of IFN-beta, a type I IFN. Additionally, maturing B cells have been shown to undergo apoptosis in response to type I IFNs including IFN-beta during differentiation. We hypothesized that the loss of B cells in the marrow of mi mice was due to the over-expression of IFN-beta as a result of heightened RANK-RANKL signaling. Creating a mouse with the mi genotype that was non-responsive to IFN-beta (lacking the type I IFNR) allowed us to test this hypothesis. These mice demonstrated an elevated number of marrow B cells and marrow precursor cells compared with mi animals possessing the type I IFNR. Intriguingly, type I IFNR-deficient wild-type animals also demonstrated an increased number of precursor cells in the marrow, but not an expansion of B220-positive pre-B cells, compared with wild type, suggesting that modulation of type I IFN responses directly controls the development of marrow constituents. |
