IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection

Abhishek Das, Gidon Ellis, Celeste Pallant, A. Ross Lopes, Pooja Khanna, Dimitra Peppa, Antony Chen, Paul Blair, Geoffrey Dusheiko, Upkar Gill, Patrick T. Kennedy, Maurizia Brunetto, Pietro Lampertico, Claudia Mauri, Mala K. Maini

Research output: Contribution to journalArticle

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+CD24hiCD38hi) ex vivo; sorted CD19+CD24hiCD38hi 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.

Original languageEnglish
Pages (from-to)3925-3935
Number of pages11
JournalJournal of Immunology
Volume189
Issue number8
DOIs
Publication statusPublished - Oct 15 2012

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection'. Together they form a unique fingerprint.

  • Cite this

    Das, A., Ellis, G., Pallant, C., Lopes, A. R., Khanna, P., Peppa, D., Chen, A., Blair, P., Dusheiko, G., Gill, U., Kennedy, P. T., Brunetto, M., Lampertico, P., Mauri, C., & Maini, M. K. (2012). IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection. Journal of Immunology, 189(8), 3925-3935. https://doi.org/10.4049/jimmunol.1103139