| First Author | Feldman AG | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 8 | Pages | e73644 |
| PubMed ID | 23991203 | Mgi Jnum | J:204543 |
| Mgi Id | MGI:5532786 | Doi | 10.1371/journal.pone.0073644 |
| Citation | Feldman AG, et al. (2013) B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia. PLoS One 8(8):e73644 |
| abstractText | A leading theory regarding the pathogenesis of biliary atresia (BA) is that bile duct injury is initiated by a virus infection, followed by an autoimmune response targeting bile ducts. In experimental models of autoimmune diseases, B cells have been shown to play an important role. The aim of this study was to determine the role of B cells in the development of biliary obstruction in the Rhesus rotavirus (RRV)-induced mouse model of BA. Wild-type (WT) and B cell-deficient (Ig-alpha(-/-)) mice received RRV shortly after birth. Ig-alpha(-/-) RRV-infected mice had significantly increased disease-free survival rate compared to WT RRV-infected BA mice (76.8% vs. 17.5%). In stark contrast to the RRV-infected BA mice, the RRV-infected Ig-alpha(-/-) mice did not have hyperbilirubinemia or bile duct obstruction. The RRV-infected Ig-alpha(-/-) mice had significantly less liver inflammation and Th1 cytokine production compared to RRV-infected WT mice. In addition, Ig-alpha(-/-) mice had significantly increased numbers of regulatory T cells (Tregs) at baseline and after RRV infection compared to WT mice. However, depletion of Tregs in Ig-alpha(-/-) mice did not induce biliary obstruction, indicating that the expanded Tregs in the Ig-alpha(-/-) mice were not the sole reason for protection from disease. Conclusion : B cell deficient Ig-alpha(-/-) mice are protected from biliary obstruction in the RRV-induced mouse model of BA, indicating a primary role of B cells in mediating disease pathology. The mechanism of protection may involve lack of B cell antigen presentation, which impairs T-cell activation and Th1 inflammation. Immune modulators that inhibit B cell function may be a new strategy for treatment of BA. |
