IL-10–Producing Regulatory B Cells in the Pathogenesis of Chronic Hepatitis B Virus Infection

2012/09/13 by Abhishek Das, Gidon Ellis, Celeste Pallant +18 · 336 citations
Immunology and Microbiology · Medicine · #Antibody #B cell #Biology #CD19 #CD24 #CD34 #CD38 #CD8 #Cell #Ex vivo #Hepatitis B #Hepatitis B Virus Studies #Hepatitis B virus #Immune Cell Function and Interaction #Immune system #Immunology #Immunotherapy and Immune Responses #In vivo #Interleukin 10 #Pathogenesis #Regulatory B cells #Stem cell #T cell #Virology #Virus

paper · pdf · doi:10.4049/jimmunol.1103139

published in The Journal of Immunology 189(8), 3925-3935 (American Association of Immunologists)

openalex publication_date 2012/09/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30

Abstract

A regulatory subset of B cells has been found to modulate immune responses in autoimmunity, infection, and cancer, but it has not been investigated in the setting of human persistent viral infection. IL-10 is elevated in patients with chronic hepatitis B virus infection (CHB), but its cellular sources and impact on antiviral T cells have not been addressed. We investigated the role of IL-10 and regulatory B cells in the pathogenesis of CHB. Serum IL-10 levels were studied longitudinally in patients with CHB undergoing spontaneous disease flares. There was a close temporal correlation between IL-10 levels and fluctuations in viral load or liver inflammation. Blockade of IL-10 in vitro rescued polyfunctional virus-specific CD8 T cell responses. To investigate the potential contribution of regulatory B cells, their frequency was measured directly ex vivo and after exposure to stimuli relevant to hepatitis B virus (HBV) (CpG or HBV Ags). IL-10-producing B cells were enriched in patients, and their frequency correlated temporally with hepatic flares, both after stimulation and directly ex vivo. Phenotypically, these cells were predominantly immature (CD19(+)CD24(hi)CD38(hi)) ex vivo; sorted CD19(+)CD24(hi)CD38(hi) cells suppressed HBV-specific CD8 T cell responses in an IL-10-dependent manner. In summary, these data reveal a novel IL-10-producing subset of B cells able to regulate T cell immunity in CHB.

Cited by

• B cells in the pathophysiology of myasthenia gravis
• NK cells: a double-edged sword in chronic hepatitis B virus infection. [europepmc]
• HIV and co-infections. [europepmc]
• Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells. [europepmc]
• The role of natural killer cells and CD8(+) T cells in hepatitis B virus infection. [europepmc]
• Host-virus interactions in hepatitis B virus infection. [europepmc]
• PD-L1 is a critical mediator of regulatory B cells and T cells in invasive breast cancer. [europepmc]
• Human regulatory B cells in health and disease: therapeutic potential. [europepmc]
• IL-10: A Multifunctional Cytokine in Viral Infections. [europepmc]
• B cells in the pathophysiology of myasthenia gravis. [europepmc]
• Circulating and intrahepatic antiviral B cells are defective in hepatitis B. [europepmc]
• A global scientific strategy to cure hepatitis B. [europepmc]
• Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). [europepmc]
• CD38, a Receptor with Multifunctional Activities: From Modulatory Functions on Regulatory Cell Subsets and Extracellular Vesicles, to a Target for Therapeutic Strategies. [europepmc]
• The Role of Dendritic Cells During Infections Caused by Highly Prevalent Viruses. [europepmc]
• Phenotypes, Functions, and Clinical Relevance of Regulatory B Cells in Cancer. [europepmc]
• The Role of Regulatory B Cells in Health and Diseases: A Systemic Review. [europepmc]
• Implication of TIGIT + human memory B cells in immune regulation. [europepmc]
• Immunosuppressive Mechanisms of Regulatory B Cells. [europepmc]
• Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression. [europepmc]
• Pathogenesis and Treatment of Cytokine Storm Induced by Infectious Diseases. [europepmc]
• Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition). [europepmc]
• Cytokines and Chemokines in HBV Infection. [europepmc]
• Human IL-10-producing B cells have diverse states that are induced from multiple B cell subsets. [europepmc]
• Friend or foe? The elusive role of hepatic stellate cells in liver cancer. [europepmc]
• Mechanisms underlying immunosuppression by regulatory cells. [europepmc]

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