| First Author | Domeier PP | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 2 | Pages | 406-418 |
| PubMed ID | 29996101 | Mgi Jnum | J:270861 |
| Mgi Id | MGI:6278805 | Doi | 10.1016/j.celrep.2018.06.046 |
| Citation | Domeier PP, et al. (2018) B-Cell-Intrinsic Type 1 Interferon Signaling Is Crucial for Loss of Tolerance and the Development of Autoreactive B Cells. Cell Rep 24(2):406-418 |
| abstractText | Type 1 interferon (T1IFN) signaling promotes inflammation and lupus pathology, but its role in autoreactive B cell development in the antibody-forming cell (AFC) and germinal center (GC) pathways is unclear. Using a lupus model that allows for focused study of the AFC and GC responses, we show that T1IFN signaling is crucial for autoreactive B cell development in the AFC and GC pathways. Through bone marrow chimeras, DNA-reactive B cell transfer, and GC-specific Cre mice, we confirm that IFNalphaR signaling in B cells promotes autoreactive B cell development into both pathways. Transcriptomic analysis reveals gene expression alterations in multiple signaling pathways in non-GC and GC B cells in the absence of IFNalphaR. Finally, we find that T1IFN signaling promotes autoreactive B cell development in the AFC and GC pathways by regulating BCR signaling. These data suggest value for anti-IFNalphaR therapy in individuals with elevated T1IFN activity before clinical disease onset. |
