title: Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties.
abstract: Whereas a B cell-transcriptional profile has been recorded for operationally tolerant kidney graft patients, the role that B cells have in this tolerance has not been reported. In this study, we analyzed the role of B cells from operationally tolerant patients, healthy volunteers, and kidney transplant recipients with stable graft function on T cell suppression. Proliferation, apoptosis, and type I proinflammatory cytokine production by effector CD4(+)CD25(-) T cells were measured after anti-CD3/anti-CD28 stimulation with or without autologous B cells. We report that B cells inhibit CD4(+)CD25(-) effector T cell response in a dose-dependent manner. This effect required B cells to interact with T-cell targets and was achieved through a granzyme B (GzmB)-dependent pathway. Tolerant recipients harbored a higher number of B cells expressing GzmB and displaying a plasma cell phenotype. Finally, GzmB(+) B-cell number was dependent on IL-21 production, and B cells from tolerant recipients but not from other patients positively regulated both the number of IL-21(+) T cells and IL-21 production, suggesting a feedback loop in tolerant recipients that increases excessive B cell activation and allows regulation to take place. These data provide insights into the characterization of B cell-mediated immunoregulation in clinical tolerance and show a potential regulatory effect of B cells on effector T cells in blood from patients with operationally tolerant kidney grafts.
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and.
authors: Mélanie
authors: M
authors: Chesneau
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France.
authors: Laure
authors: L
authors: Michel
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France.
authors: Emilie
authors: E
authors: Dugast
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and.
authors: Alexis
authors: A
authors: Chenouard
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and.
authors: Daniel
authors: D
authors: Baron
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France;
authors: Annaïck
authors: A
authors: Pallier
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and.
authors: Justine
authors: J
authors: Durand
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and.
authors: Faouzi
authors: F
authors: Braza
authors: Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France.
authors: Pierrick
authors: P
authors: Guerif
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France.
authors: David-Axel
authors: DA
authors: Laplaud
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France.
authors: Jean-Paul
authors: JP
authors: Soulillou
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France.
authors: Magali
authors: M
authors: Giral
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and.
authors: Nicolas
authors: N
authors: Degauque
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and.
authors: Elise
authors: E
authors: Chiffoleau
authors: Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France; Faculty of Medicine, Nantes University, Nantes, France; and Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France sophie.brouard@univ-nantes.fr.
authors: Sophie
authors: S
authors: Brouard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D023001:Transplantation Tolerance
keywords: B cells; apoptosis; granzyme B; kidney transplantation; regulation; tolerance
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