Entering the spotlight: hepatitis B surface antigen–specific B cells

Thimme, Robert

doi:10.1172/jci124098

Cited by 16 publications

(11 citation statements)

References 21 publications

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“…Recent studies demonstrated HBsAg-specific humoral response in the circulation of CHB patients and found that HBsAg-specific B cells contain atMBCs cells expressing high PD-1 and blockade of PD-1 partially restored the function of HBsAg-specific B cells [ 68 ]. Moreover, addition of IL-2, IL-21, and CD40L is also useful for the partial recovery of HBsAg-specific B cell function [ 24 , 68 , 83 ]. Since anti-HBs neutralizing antibodies are critical to control viral infection, impaired anti-HBs antibody production leads to persistent HBV infection.…”

Section: Innate and Adaptive Immune Response Against Hbv Infectionmentioning

confidence: 99%

Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression

Khanam

Chua

Kottilil

2021

IJMS

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More than 250 million people are living with chronic hepatitis B despite the availability of highly effective vaccines and oral antivirals. Although innate and adaptive immune cells play crucial roles in controlling hepatitis B virus (HBV) infection, they are also accountable for inflammation and subsequently cause liver pathologies. During the initial phase of HBV infection, innate immunity is triggered leading to antiviral cytokines production, followed by activation and intrahepatic recruitment of the adaptive immune system resulting in successful virus elimination. In chronic HBV infection, significant alterations in both innate and adaptive immunity including expansion of regulatory cells, overexpression of co-inhibitory receptors, presence of abundant inflammatory mediators, and modifications in immune cell derived exosome release and function occurs, which overpower antiviral response leading to persistent viral infection and subsequent immune pathologies associated with disease progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. In this review, we discuss the current knowledge of innate and adaptive immune cells transformations that are associated with immunopathogenesis and disease outcome in CHB patients.

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Section: Innate and Adaptive Immune Response Against Hbv Infectionmentioning

confidence: 99%

Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression

Khanam

Chua

Kottilil

2021

IJMS

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“…However, the cellular phenotype was similar to CD21− CD27− atypical memory B cells (atMBCs), which express high levels of inhibitory receptors, such as programmed cell death receptor-1 (PD-1). Moreover, HBsAg-specific B cells isolated from HBV-infected patients could not efficiently expand and mature into antibody-secreting cells in vitro , whereas a PD-1 blockade or the addition of IL-2, IL-21, and CD40L may partially restore the function of HBsAg-specific B cells ( 32 , 42 , 43 ). Since anti-HBs antibodies can function as protective neutralizing antibodies to block HBV entry or replication, it can be inferred that the dysfunction of anti-HBs secretion by B cells is beneficial for the maintenance of high levels of HBsAg and hinders HBV clearance.…”

Section: Antibody Production Function Of B Cellsmentioning

confidence: 99%

“…In addition, according to the initial ELISpot examination of plasma cell formation, there were fewer global B cells and plasma cells isolated from the peripheral blood of CHB patients compared with the vaccinated controls ( 65 , 66 ). One reason for this observation may be the enrichment of atMBCs in the liver and functional impairment of atMBCs’ differentiation into antibody-secreting plasma cells ( 32 , 43 ). Another reason might be the enrichment of these virus-specific B cells in the liver of patients, which is not conducive to migration to the bone marrow and formation of long-lived plasma cells ( 32 ).…”

Section: Antibody Production Function Of B Cellsmentioning

confidence: 99%

The Multiple Functions of B Cells in Chronic HBV Infection

Cai

Yin

2020

Front. Immunol.

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Chronic hepatitis B virus (HBV) infection is one of the main causes of liver diseases, of which the natural history and clinical outcomes are associated with the role of B cells. As humoral immune cells, B cells play a critical role in the process of anti-HBV antibody production. In addition, some studies have also characterized other B cell subsets involved in antigen presentation and regulating the immune response beyond antibody secretion. However, not all B cell subsets play a positive role in the immune response to chronic HBV infection, and various B cell subsets jointly mediate persistent HBV infection, tolerance, and liver damage. Thus, we further sought to elucidate the multiple functions of B cells to gain novel insight into the understanding of chronic hepatitis B (CHB) pathogenesis. We also reviewed the current immunotherapies targeting B cells to explore novel therapeutic interventions for the treatment of chronic HBV infection.

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“…For example, it was proposed that B cell intrinsic mechanisms as well as a reduced or dysregulated help from CD4+ T cells, especially T follicular helper (Tfh) cells, might contribute to this scenario [32,33]. Recently, the detection of hepatitis B virus (HBV)-specific B cells through flow cytometry was made possible by the use of fluorochrome-coupled HBsAg and HBV core molecules as 'traits' [34][35][36][37]. A similar methodological development for HCV-specific B cells, however, is hindered by the lack of knowledge regarding E1E2 structural biology.…”

Section: Antibody Responsementioning

confidence: 99%

Adaptive Immune Response against Hepatitis C Virus

Kemming

Thimme

2020

IJMS

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A functional adaptive immune response is the major determinant for clearance of hepatitis C virus (HCV) infection. However, in the majority of patients, this response fails and persistent infection evolves. Here, we dissect the HCV-specific key players of adaptive immunity, namely B cells and T cells, and describe factors that affect infection outcome. Once chronic infection is established, continuous exposure to HCV antigens affects functionality, phenotype, transcriptional program, metabolism, and the epigenetics of the adaptive immune cells. In addition, viral escape mutations contribute to the failure of adaptive antiviral immunity. Direct-acting antivirals (DAA) can mediate HCV clearance in almost all patients with chronic HCV infection, however, defects in adaptive immune cell populations remain, only limited functional memory is obtained and reinfection of cured individuals is possible. Thus, to avoid potential reinfection and achieve global elimination of HCV infections, a prophylactic vaccine is needed. Recent vaccine trials could induce HCV-specific immunity but failed to protect from persistent infection. Thus, lessons from natural protection from persistent infection, DAA-mediated cure, and non-protective vaccination trials might lead the way to successful vaccination strategies in the future.

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Entering the spotlight: hepatitis B surface antigen–specific B cells

Cited by 16 publications

References 21 publications

Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression

Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression

The Multiple Functions of B Cells in Chronic HBV Infection

Adaptive Immune Response against Hepatitis C Virus

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