Dysregulated Humoral Immune Response To Hepatitis B Surface Antigen Promotes HBV Persistence

Chronic HBV infection continues to be a major public health issue worldwide.In China,about 10 percent of people were infected with HBV,and somebody even carried for life.Most adults can quickly remove the virus after HBV infection,which presents a state of acute infection,but infants and young children can not effectively remove viruses after infection,which presents a state of chronic HBV infection.Chronic HBV infection not only causes severe psychological burden,but may also induce liver fibrosis and liver cancer.Although the pathogenesis of chronic HBV infection has been studied for many years,we still lack an ideal therapy to cure it.Using the mouse models of acute and chronic HBV infection,we found that the anti-viral humoral immune responses,which were largely ignored in the past studies,played an important role in HBV clearance.Through literature research,we found an HBV transfection model,which take HBV genome into mouse through hydrodynamic injection(HDI).Previous studies have found that the exhaustion of CD8~+T cells and NK cells contributed to the pathogenesis of chronic HBV infection,but pay little attention to humoral immunity.Our study focused on anti-HBV humoral immune responses,and our results were as follows:1.Deletion of B cells inhibited the clearance of HBV antigens.2.Tfh cells from HBsAg-immunized mouse could induce the differentiation of GC B cells,and accelerated clearance of HBV.3.Deletion of Treg cells could improve humoral immunity,which could accelerate clearance of HBV.4.Blocking CTLA-4 on Treg cells could also result in clearance of HBV.5.Peripheral blood cells from chronic HBV patients,which were treated with anti-CTLA-4 blocking antibody,can induce the differentiation of Tfh cells after stimulation of HBsAg polypeptide.In studies of HBV-infected mice model and blood samples from HBV-infected patients,we found that the effective anti-HBV humoral immune response,especially anti-HBs production,was required for HBV clearance,and that this response was inhibited by Treg cells during chronic HBV infection.Inhibiting Treg cell function using blocking antibody against CTLA-4 restored the ability of Tfh/GC B cells to clear HBV,this approach might be developed for treatment of patients with chronic HBV infection.