CD20+ B cell infiltration in a mouse model for HBV-associated liver fibrosis depends on genetic background
CD20+ B cell infiltration in a mouse model for HBV-associated liver fibrosis depends on genetic background
复制标题
HBV 相关肝纤维化小鼠模型中 CD20 B 细胞浸润取决于遗传背景
DOI：
10.1055/s-0031-1285621
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
E Roeb
中科院分区：
文献类型：
--
作者：
J Stiefel;Y Churin;M Roderfeld;K Kopsch;D Glebe;E Roeb
研究方法：在出生后的不同时间点（3、6和12个月）处死在肝脏中产生HBV大包膜多肽和肝炎B表面抗原（HBsAg）的C57 BL/6与BALB B/c转基因小鼠及其非转基因同窝出生小鼠。以血清谷丙转氨酶（ALT）活性为指标检测肝损伤程度。通过天狼星红染色和实时PCR测量胶原表达来估计肝纤维化。招募T和B淋巴细胞进行了研究，使用抗-CD 3和抗-CD 20 antibody，respectively.Results：ALT活性较高的tg小鼠在这两个遗传背景相比，相应的同窝出生。组织学和免疫荧光分析显示tg小鼠有明显的炎症和纤维化。有趣的是，与tg（C57 BL/6）相比，我们观察到tg（BALB/c）中更显著的纤维化。与非转基因同窝出生小鼠相比，BALB/c-tg和C57 BL/6-tg小鼠的肝脏中B和T细胞浸润增加。结论：Tg（BALB/c）模型较tg（C57 BL/6）模型更适合于肝纤维化的研究。
Methods: C57BL/6 versus BALB/c transgenic mice producing HBV large envelope polypeptide and hepatitis B surface antigen (HBsAg) in the liver and their non-transgenic littermates were sacrificed at different time points after birth (3, 6 and 12 months). The extent of liver injury was examined by serum alanine transaminase (ALT) activity. Hepatic fibrosis was estimated by Sirius Red staining and measurement of collagen expression by real-time PCR. Recruitment of T and B lymphocytes was studied using anti-CD3 and anti-CD20 antibody, respectively.Results: ALT activity was higher in tg mice on both genetic backgrounds compared to corresponding littermates. Histological and immunofluorescence analyses of liver tissue revealed significant inflammation and fibrosis in tg mice. Interestingly we observed a more prominent fibrosis in tg (BALB/c) compared to tg (C57BL/6). Both, BALB/c-tg and C57BL/6-tg mice, showed heightened B and T cell infiltration compared to non-transgenic littermates in the liver. However, the number of CD20-positive cells was significantly increased in tg (BALB/c) compared to tg (C57BL/6).Conclusions:Tg (BALB/c) seems to be more appropriate to study fibrosis than tg (C57BL/6) model.