B cells promote hepatic inflammation, biliary cyst formation, and salivary gland inflammation in the NOD.c3c4 model of autoimmune cholangitis.

Abstract:

:There are now several murine models of autoimmune cholangitis that have features both similar and distinct from human PBC. One such model, the NOD.c3c4 mouse, manifests portal cell infiltrates, anti-mitochondrial antibodies but also biliary cysts. The biliary cysts are not a component of PBC and not found in the other murine models. To address the immunopathology in these mice, we generated genetically B cell deficient Igμ(-/-) NOD.c3c4 mice and compared the immunopathology of these animals to control B cell sufficient NOD.c3c4 mice. B cell deficient mice demonstrated decreased number of non-B cells in the liver accompanied by reduced numbers of activated natural killer cells. The degree of granuloma formation and bile duct damage were comparable to NOD.c3c4 mice. In contrast, liver inflammation, biliary cyst formation and salivary gland inflammation was significantly attenuated in these B cell deficient mice. In conclusion, B cells play a critical role in promoting liver inflammation and also contribute to cyst formation as well as salivary gland pathology in autoimmune NOD.c3c4 mice, illustrating a critical role of B cells in modulating specific organ pathology and, in particular, in exacerbating both the biliary disease and the sialadenitis.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Moritoki Y,Tsuda M,Tsuneyama K,Zhang W,Yoshida K,Lian ZX,Yang GX,Ridgway WM,Wicker LS,Ansari AA,Gershwin ME

doi

10.1016/j.cellimm.2011.01.005

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

16-23

issue

1

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(11)00015-3

journal_volume

268

pub_type

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