Study On The Effect Of B Lymphocyte On The Development And Progression Of Hepatic Tumor

Objective: Immunocompromised patients with cancer is the universal clinical features,Immune escape is an important mechanism of rapid deterioration of the tumor,the detailed molecular mechanism remain to be elucidated.This study was designed to investigate the effect of B lymphocytes on the development of HCC under noninflammatory conditions.Methods: By studying a mouse model of hepatic tumor induced by hepatocyte-specific expression of the H-ras12 V oncogene without obvious inflammation,To explore the changes and the roles of B,T lymphocytes and Ig G1/2 in the progression of hepatic tumors.1.3,5 and 9 month-old H-ras12 V transgenic male mice(Tg)andC57BL/6J wild type mice(Wt)were subjected to autopsy,and the pathological changes of the liver were observed and counted.2.The ratio of subtypes and activation of T and B lymphocytes in peripheral white blood cells of 3,5 and 9 month-old normal wild type C57BL/6J(non-transgenic)and H-ras12 V transgenic males were detected by using flow cytometry(FCM).3.The serum IgG1/2 levels of 3,5 and 9 month-old Wt and Tg males were detected by ELISA.4.The heterozygous Tg were obtained by mating Tg with Wt,and the ratio of B and T lymphocytes in peripheral blood and the progression of hepatic tumor were detected compared with homozygous Tg at 9-month-old.5.The ratio of B and T lymphocytes in peripheral blood and the progression of hepatic tumor were detected in 9-month-old H-ras12 V transgenic mice after 6 month of treatment with PCI32765,a potent Bruton's tyrosine kinase(BTK)inhibitor for suppressing B cell proliferation and activation.6.The ratio of B and T lymphocytes in peripheral blood and the progression of hepatic tumor were detected in 9-month-old H-ras12 V transgenic mice after 6 month of treatment with IGF-1.Results:1.The number of B cells,but not T cells,progressively and significantly decreased in 3-and 5-month-old transgenic mice(Tg)compared with non-transgenic mice.2.Together with the decreased B cells numbers,serum IgG1/2 also significantly decreased in 5-and 9-month-old Tg.B cell numbers and IgG1/2 concentrations negatively correlate to the progression of hepatic tumors and hepatocyte-specific expression levels of the ras oncogene.3.Homozygous Tg showed significantly higher B cells numbers and IgG2 levels,accompanied by significantly lower incidences of liver nodules but not adenomas and carcinomas compared with heterozygous Tg.4.PCI32765 significantly reduces B cell numbers and IgG2 levels,accompanied by an increased incidence of hepatic nodules,but not adenomas and carcinomas.5.IGF-1 significantlyincreases B cell numbers and IgG2 levels,accompanied by a decreased incidence of hepatic nodules,but not adenomas.Conclusion:1.B cells and IgG2 may play important roles in suppressing hepatic tumorigenesis,but not development.2.Hepatocyte-specific expression of the ras oncogene may play roles in suppressing B cells,while developed hepatic tumors suppress both B and T cells,which in turn favor immune evasion and thus promote tumor progression.