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

Author(s):Show less -

Silva, Hernandez M. ^{[1, 2]} ; Takenaka, Maisa C. S. ^{[1, 2]} ; Moraes-Vieira, Pedro M. M. ^{[1, 3, 2]} ; Monteiro, Sandra M. ^{[1, 2]} ; Hernandez, Maristela O. ^{[1, 2]} ; Chaara, Wahiba ^{[4, 5, 6]} ; Six, Adrien ^{[4, 5]} ; Agena, Fabiana ^[6] ; Sesterheim, Patricia ^{[7, 2]} ; Barbe-Tuana, Florencia Maria ^{[7, 2]} ; Saitovitch, David ^{[7, 2]} ; Lemos, Francine ^[8] ; Kalil, Jorge ^{[1, 2]} ; Coelho, Veronica ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Med, Immunol Lab, Heart Inst InCor, Sao Paulo - Brazil

^[2] INCT Natl Inst Sci & Technol, Inst Invest Immunol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Sao Paulo - Brazil

^[4] Univ Paris 06, UMR 7211, Paris - France

^[5] CNRS, UMR 7211, Paris - France

^[6] Hop La Pitie Salpetriere, AP HP, Serv Biotherapie, Paris - France

^[7] Pontificia Univ Catolica Rio Grande do Sul, Div Nephrol, Sao Lucas Hosp, Porto Alegre, RS - Brazil

^[8] Univ Sao Paulo, Sch Med, Div Nephrol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Molecular Medicine; v. 18, n. 5, p. 733-743, MAY 2012.
• Web of Science Citations: 51

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-c ell 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. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00281 (AU)