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B lymphocytes repress hepatic tumorigenesis but not development in Hras12V transgenic mice
Author(s) -
Wang Kangwei,
Nie Xin,
Rong Zhuona,
Fan Tingting,
Li Juan,
Wang Xinxin,
Li Huiling,
Dong Jianyi,
Chen Jun,
Wang Fujin,
Wang Jingyu,
Wang Aiguo
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30823
Subject(s) - medicine , endocrinology , carcinogenesis , oncogene , biology , hepatocyte , genetically modified mouse , transgene , adenoma , b cell , cancer research , cell cycle , cancer , immunology , antibody , gene , biochemistry , in vitro
Increasing reports show noninflammation underlying HCC, challenging our understanding of the roles of the immune system in hepatocarcinogenesis. By exploring a mouse model of hepatic tumor induced by hepatocyte‐specific expression of the Hras12V oncogene without obvious inflammation, we found that the proportion of B cells, but not T cells, progressively and significantly decreased in 3, 5‐month‐old transgenic mice (Tg) compared with non‐transgenic mice. Notably, the proportions of total and activated B and T cells all significantly decreased in 9‐month‐old Tg with multiple massive hepatic tumors. Together with the decreased B cell proportion, serum IgG1/2 also significantly decreased in 5, 9‐month‐old Tg. Interestingly, homozygous Tg showed significantly higher B cell proportion and IgG2 levels, accompanied by significantly lower incidences of liver nodules but not adenomas and carcinomas compared with heterozygous Tg. Treatment of Tg with PCI‐32765, a potent Bruton's tyrosine kinase (BTK) inhibitor for suppressing B cell proliferation and activation, significantly decreased the B cell proportion and IgG2 levels, accompanied by a significantly higher incidence of liver nodules, but had no effects on adenoma and carcinoma. Treatment of Tg with insulin‐like growth factor 1 (IGF‐1) significantly increased the B cell proportion and IgG2 levels, accompanied by a significantly lower incidence of liver nodules and carcinoma, but had no effects on adenoma. Conclusively, B cells and IgG2 may play important roles in suppressing hepatic tumorigenesis, but not development. In addition, hepatocyte‐specific expression of the ras oncogene may play roles in suppressing B cells, while developed hepatic tumors suppress both B and T cells.