| First Author | Mayne CG | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 2 | Pages | 587-98 |
| PubMed ID | 18200501 | Mgi Jnum | J:131359 |
| Mgi Id | MGI:3773555 | Doi | 10.1002/eji.200737817 |
| Citation | Mayne CG, et al. (2008) Systemic autoimmunity in BAFF-R-mutant A/WySnJ strain mice. Eur J Immunol 38(2):587-98 |
| abstractText | Systemic lupus erythematosis is an autoimmune disease of unknown etiology. Lupus pathology is thought to reflect autoantibody-mediated damage due to a failure of B lymphocyte tolerance. Since excessive B cell-activating factor belonging to the TNF family (BAFF) expression correlates with human and murine lupus, and BAFF signals B cell survival through BAFF-R, it is believed that excessive BAFF-R signaling can subvert B cell tolerance and facilitate lupus development. Here we report the unexpected finding that BAFF-R-mutant A/WySnJ mice develop a lupus-like syndrome. These mice carry the B cell maturation defect-1 (Bcmd-1) mutant allele of the Baffr gene. Bcmd-1 causes premature B cell death and profound B cell deficiency. Despite having 90% fewer splenic B cells than normal mice, A/WySnJ mice had an 18-fold increased frequency of splenocytes secreting IgM antibodies to dsDNA, and increased amounts of circulating IgM and IgG to dsDNA by 9 months of age. By age 11 months, most A/WySnJ mice displayed renal pathology characteristic of lupus, including proteinuria as well as periodic acid-Schiff-positive deposits and glomerular capillary bed destruction. Importantly, we genetically linked this autoimmunity to Bcmd-1, since congenic AW.Baffr(+/+) mice carrying a wild-type allele developed none of these phenotypes. Our data provide the first evidence linking altered BAFF-R signaling to the development of B cell-mediated autoimmunity. |
