Dynamic Changes And Functions Of Follicular Helper T Cells(Tfh) In The Progression Of Chronic Hepatitis B

Hepatitis B virus(HBV)infection remains an important public health problem in China and even around the world.Current treatments only achieve functional cure in10%of patients,so there is an urgent need to find new strategies to treat Chronic hepatitis B.HBV surface antibody(HBs Ab)was one of the key factors to promote functional recovery of CHB patients.HBs Ab are essential to eliminate viral infection,and impaired B cell immune function in CHB patients is associated with HBV infection progression.T follicular help cells(Tfh)are a new subset of CD4~+T cells,which can not only promote the generation of Germinal center(GC),but also directly interact with B cells in GC to promote the proliferation and differentiation of B cells and participate in the production of HBs Ab.More insights about the dysregulation of B cells and Tfh cells might help to find new immunotherapy strategies for CHB patients.Here,the causes of antibody secretion dysfunction in CHB patients were investigated from B and Tfh cells.Compared with healthy subjects,total B cells increased abnormally in CHB patients,while double negative B cells increased significantly,marginal zone-like B cells decreased significantly,and specific marginal zone-like B cells and double negative B cells increased significantly,suggesting that these two groups of cells may be involved in the process of B cell dysfunction.HBe Ag positive immune activation,HBe Ag negative immune reactivation,immune tolerance,and inactive CHB phase patients were studied,and HBs Ag-specific B cells were significantly increased in HBs Ag-negative immune reactivation patients,while significantly decreased in immune tolerance patients.The number of B cells that secrete surface antibodies was significantly reduced in CHB patients by ELISpot assay.Meanwhile,Tfh cell study found that total Tfh and Tfh2 cells increased in patients with CHB,while Tfh1 cells decreased significantly,suggesting that the frequency disorder of Tfh cell subsets may be related to B cell dysfunction.Subsequently,activated and quiescent Tfh cells were analyzed,and it was found that activated Tfh1 and Tfh2 cells were significantly increased in CHB patients.Total quiescent and Tfh cells of different subgroups were significantly decreased.Correlation analysis showed that activated and quiescent Tfh2 cells may be involved in the differentiation of HBs Ag~+specific B cells.Finally,HBs Ag~+Tfh cells were analyzed and specific Tfh and Tfh1 cells were significantly increased in patients with chronic hepatitis B.In conclusion,this study confirmed the frequency disturbance of B cell and Tfh cell subsets in CHB patients,which may be involved in the dysfunction of specific B cell surface antibody secretion.This study provides a new immune strategy for the treatment of chronic hepatitis B from the perspective of B cell and Tfh cell subpopulations.