title: IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection.
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.
authors.affiliation: Division of Infection and Immunity, University College London, London WC1E 6JF, United Kingdom.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Das
authors.forename: Gidon
authors.initials: G
authors.lastname: Ellis
authors.forename: Celeste
authors.initials: C
authors.lastname: Pallant
authors.forename: A Ross
authors.initials: AR
authors.lastname: Lopes
authors.forename: Pooja
authors.initials: P
authors.lastname: Khanna
authors.forename: Dimitra
authors.initials: D
authors.lastname: Peppa
authors.forename: Antony
authors.initials: A
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Blair
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Dusheiko
authors.forename: Upkar
authors.initials: U
authors.lastname: Gill
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Kennedy
authors.forename: Maurizia
authors.initials: M
authors.lastname: Brunetto
authors.forename: Pietro
authors.initials: P
authors.lastname: Lampertico
authors.forename: Claudia
authors.initials: C
authors.lastname: Mauri
authors.forename: Mala K
authors.initials: MK
authors.lastname: Maini
mesh_terms: D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10