title: Preserving the B-cell compartment favors operational tolerance in human renal transplantation.
abstract: Transplanted individuals in operational tolerance (OT) maintain long-term stable graft function after completely stopping immunosuppression. Understanding the mechanisms involved in OT can provide valuable information about pathways to human transplantation tolerance. Here we report that operationally tolerant individuals display quantitative and functional preservation of the B-cell compartment in renal transplantation. OT exhibited normal numbers of circulating total B cells, naive, memory and regulatory B cells (Bregs) as well as preserved B-cell receptor repertoire, similar to healthy individuals. In addition, OT also displayed conserved capacity to activate the cluster of differentiation 40 (CD40)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in Bregs, in contrast, with chronic rejection. Rather than expansion or higher activation, we show that the preservation of the B-cell compartment favors OT.
authors.affiliation: Laboratory of Immunology, Heart Institute-InCor, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Hernandez M
authors.initials: HM
authors.lastname: Silva
authors.forename: Maisa C S
authors.initials: MC
authors.lastname: Takenaka
authors.forename: Pedro M M
authors.initials: PM
authors.lastname: Moraes-Vieira
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Monteiro
authors.forename: Maristela O
authors.initials: MO
authors.lastname: Hernandez
authors.forename: Wahiba
authors.initials: W
authors.lastname: Chaara
authors.forename: Adrien
authors.initials: A
authors.lastname: Six
authors.forename: Fabiana
authors.initials: F
authors.lastname: Agena
authors.forename: Patrícia
authors.initials: P
authors.lastname: Sesterheim
authors.forename: Florencia Maria
authors.initials: FM
authors.lastname: Barbé-Tuana
authors.forename: David
authors.initials: D
authors.lastname: Saitovitch
authors.forename: Francine
authors.initials: F
authors.lastname: Lemos
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Verônica
authors.initials: V
authors.lastname: Coelho
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D011947:Receptors, Antigen, B-Cell; D050796:STAT3 Transcription Factor