Partial rescue of B cells in microphthalmic osteopetrotic marrow by loss of response to type I IFNs.
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.
Roundy
Kirstin M
KM
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Spangrude
Gerald
G
Weis
Janis J
JJ
Weis
John H
JH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016899:Interferon-beta / Q000172:deficiency / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D051739:Microphthalmia-Associated Transcription Factor / Q000172:deficiency / Q000276:immunology*; D008850:Microphthalmos / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010022:Osteopetrosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016899:Interferon-beta; D017493:Leukocyte Common Antigens