B Cell Deficient Mice Are Protected from Biliary Obstruction in the Rotavirus-Induced Mouse Model of Biliary Atresia.docVIP

B Cell Deficient Mice Are Protected from Biliary Obstruction in the Rotavirus-Induced Mouse Model of Biliary Atresia Amy G. Feldman , Rebecca M. Tucker , Erika K. Fenner , Roberta Pelanda , Cara L. Mack 1* 2 2 3 1,2 1 Department of Pediatrics, Section of Pediatric Gastroenterology, Children’s Hospital, Colorado, United States of America, Aurora, Colorado, United States of America, 2 Departments of Medicine and Immunology, University of Colorado School of Medicine, Aurora, Colorado, United States of America, 3 Integrated Department of Immunology, National Jewish Health, Denver, Colorado, United States of America Abstract 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-α 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-α mice did not have hyperbilirubinemia or bile duct obstruction. The RRV- infected Ig-α mice had significantly less liver inflammation and Th1 cytokine production compared to RRV-infected WT mice. In addition, Ig-α 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-α mice did not induce biliary obstruction, indicating that the expanded Tregs in