Preserving the B-Cell Compartment Favors Operational Tolerance in Human Renal Transplantation

Hernandez M Silva (1, 2) , Maisa Takenaka (1, 2) , Pedro Moraes-Vieira (2, 1) , Sandra Monteiro (1, 2) , Maristela O Hernandez (1, 2) , Wahiba Chaara (3, 4, 5) , Adrien Six (3, 4) , Fabiana Agena (5) , Patrícia Sesterheim (6) , Florencia Maria Barbé-Tuana (6) , David Saitovitch (6) , Francine Lemos (1) , Jorge Kalil (1, 2) , Verônica Coelho (1, 2)

1 USP - Universidade de São Paulo = University of São Paulo
2 III - Institute for Investigation in Immunology
3 I3 - Immunologie - Immunopathologie - Immunothérapie
4 SU FM - Sorbonne Université - Faculté de Médecine
5 CHU Pitié-Salpêtrière [AP-HP]
6 PUC-RS - Pontifícia Universidade Católica do Rio Grande do Sul [Brasil] = Pontifical Catholic University of Rio Grande do Sul [Brazil] = Université catholique pontificale de Rio Grande do Sul [Brésil]

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.

Domaines: Immunologie; Chirurgie; Urologie et Néphrologie

Hernandez M Silva, Maisa Takenaka, Pedro Moraes-Vieira, Sandra Monteiro, Maristela O Hernandez, et al.. Preserving the B-Cell Compartment Favors Operational Tolerance in Human Renal Transplantation. Molecular Medicine, 2012, 18 (5), pp.733-743. ⟨10.2119/molmed.2011.00281⟩. ⟨hal-01959589⟩