title: IL-10-produced by human transitional B-cells down-regulates CD86 expression on B-cells leading to inhibition of CD4+T-cell responses.
abstract: A novel subset of human regulatory B-cells has recently been described. They arise from within the transitional B-cell subpopulation and are characterised by the production of IL-10. They appear to be of significant importance in regulating T-cell immunity in vivo. Despite this important function, the molecular mechanisms by which they control T-cell activation are incompletely defined. Here we show that transitional B-cells produced more IL-10 and expressed higher levels of IL-10 receptor after CD40 engagement compared to other B-cell subsets. Furthermore, under this stimulatory condition, CD86 expressed by transitional B-cells was down regulated and T-cell proliferation was reduced. We provide evidence to demonstrate that the down-regulation of CD86 expression by transitional B-cells was due to the autocrine effect of IL-10, which in turn leads to decreased T-cell proliferation and TNF-α production. This analysis was further extended to peripheral B-cells in kidney transplant recipients. We observed that B-cells from patients tolerant to the graft maintained higher IL-10 production after CD40 ligation, which correlates with lower CD86 expression compared to patients with chronic rejection. Hence, the results obtained in this study shed light on a new alternative mechanism by which transitional B-cells inhibit T-cell proliferation and cytokine production.
authors.affiliation: King's College London, MRC Centre for Transplantation, London, United Kingdom.
authors.forename: Estefania
authors.initials: E
authors.lastname: Nova-Lamperti
authors.affiliation: King's College London, MRC Centre for Transplantation, London, United Kingdom.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Fanelli
authors.affiliation: King's College London, MRC Centre for Transplantation, London, United Kingdom.
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Becker
authors.affiliation: BRC Flow Cytometry Laboratory, Guy's Hospital, London, United Kingdom.
authors.forename: Prabhjoat
authors.initials: P
authors.lastname: Chana
authors.affiliation: King's College London, MRC Centre for Transplantation, London, United Kingdom.
authors.forename: Raul
authors.initials: R
authors.lastname: Elgueta
authors.affiliation: King's College London, MRC Centre for Transplantation, London, United Kingdom.
authors.forename: Philippa C
authors.initials: PC
authors.lastname: Dodd
authors.affiliation: King's College London, MRC Centre for Transplantation, London, United Kingdom.|NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, Guy's Hospital, London, United Kingdom.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Lord
authors.affiliation: King's College London, MRC Centre for Transplantation, London, United Kingdom.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: King's College London, MRC Centre for Transplantation, London, United Kingdom.|NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, Guy's Hospital, London, United Kingdom.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Hernandez-Fuentes
mesh_terms: D000328:Adult; D000368:Aged; D019898:Autocrine Communication; D051940:B7-2 Antigen / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism*; D055815:Young Adult
chemical_list: D051940:B7-2 Antigen; C508609:IL10 protein, human; D016753:Interleukin-10