Journal Article

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

Mack, Cara L., Pelanda, Roberta, Feldman, Amy G., Tucker, Rebecca M., Fenner, Erika K.

2013

Overview

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(-/-)) mice received RRV shortly after birth. Ig-α(-/-) 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-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 the Ig-α(-/-) mice were not the sole reason for protection from disease. Conclusion : B cell deficient Ig-α(-/-) 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animal models / Animals / Antigen presentation / Antigen-Presenting Cells - immunology / Antigens / Autoimmune diseases / Autoimmunity / B cells / B-Lymphocytes - immunology / Bile / Bile ducts / Biliary atresia / Biliary Atresia - complications / Biliary Atresia - immunology / Biliary Atresia - virology / Cell activation / Cholestasis - prevention & control / Comparative analysis / Departments / Diabetes / Disease / Disease Models, Animal / Flow Cytometry / Gastroenterology / Health aspects / Hyperbilirubinemia / Immunoglobulins / Immunology / Immunomodulation / Immunoregulation / Infection / Infections / Laboratory animals / Liver / Lymphocytes / Lymphocytes B / Lymphocytes T / Medical research / Medicine / Mice / Modulators / Multiple sclerosis / Pathogenesis / Pediatrics / Rheumatoid arthritis / Rheumatology / Rodents / Rotavirus / Rotavirus - pathogenicity / Survival / T cell receptors / T cells / T-Lymphocytes, Regulatory - immunology / Transplants & implants / Viral infections / Viruses