title: Increased CD40 Ligation and Reduced BCR Signalling Leads to Higher IL-10 Production in B Cells From Tolerant Kidney Transplant Patients.
abstract: An increased percentage of peripheral transitional B cells producing IL-10 has been observed in patients tolerant to kidney allografts. In healthy volunteers, the balance between the CD40 and B-cell receptor (BCR) signalling modulated IL-10 production by B cells, with stimulation via the BCR decreasing CD40-mediated IL-10 production. In this study, we evaluate whether in tolerant kidney transplant patients, the increased IL-10 production by B cells was due to an altered CD40 and/or BCR signalling.
  
  
  
  B cells obtained from a new cohort of tolerant renal transplant recipients and those from age- and sex-matched healthy volunteers were activated via CD40 and BCR, either alone or in combination.
  
  
  
  In tolerant patients, we observed higher percentages of B cells producing IL-10 after CD40 ligation and higher expression of CD40L on activated T cells compared with healthy controls. Furthermore, B cells from tolerant recipients had reduced extracellular signal-regulated kinase signalling after BCR-mediated activation compared with healthy controls. In keeping with this, combining BCR signalling with CD40 ligation did not reduce IL-10 secretion as was observed in healthy control transitional B cells.
  
  
  
  Altogether, our data suggest that the altered response of B cells in tolerant recipients may contribute to long-term stable graft acceptance.
authors.affiliation: 1 King's College London, MRC Centre for Transplantation, London, United Kingdom. 2 BRC Flow Cytometry Laboratory, Guy's Hospital, London, United Kingdom. 3 NIHR Comprehensive Biomedical Research Centre at Guy's and St Thomas' Hospital, London, United Kingdom. 4 King's Health Partners, London, United Kingdom.
authors.forename: Estefania
authors.initials: E
authors.lastname: Nova-Lamperti
authors.forename: Prabhjoat
authors.initials: P
authors.lastname: Chana
authors.forename: Paula
authors.initials: P
authors.lastname: Mobillo
authors.forename: Manohursingh
authors.initials: M
authors.lastname: Runglall
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Kamra
authors.forename: Reuben
authors.initials: R
authors.lastname: McGregor
authors.forename: Graham M
authors.initials: GM
authors.lastname: Lord
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Maria P
authors.initials: MP
authors.lastname: Hernandez-Fuentes
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000494:pharmacology; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D023001:Transplantation Tolerance; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D019013:CD40 Antigens; C508609:IL10 protein, human; D007376:Interleukin-2; D011947:Receptors, Antigen, B-Cell; D016753:Interleukin-10; D023201:CD40 Ligand; D048049:Extracellular Signal-Regulated MAP Kinases