title: B-cell tolerance in transplantation: is repertoire remodeling the answer?
abstract: T lymphocytes are the primary targets of immunotherapy in clinical transplantation; however, B lymphocytes and their secreted alloantibodies are also highly detrimental to the allograft. Therefore, the achievement of sustained organ transplant survival will likely require the induction of B-lymphocyte tolerance. During development, acquisition of B-cell tolerance to self-antigens relies on clonal deletion in the early stages of B-cell compartment ontogeny. We contend that this mechanism should be recapitulated in the setting of alloantigens and organ transplantation to eliminate the alloreactive B-cell subset from the recipient. Clinically feasible targets of B-cell-directed immunotherapy, such as CD20 and B-lymphocyte stimulator (BLyS), should drive upcoming clinical trials aimed at remodeling the recipient B-cell repertoire.
authors.affiliation: 329 Stemmler Hall, 36th and Hamilton Walk, University of Pennsylvania School of Medicine, Harrison Department of Surgical Research, Philadelphia, PA 19104, USA, Tel.: +1 215 400 1806.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Parsons
authors.forename: Kumar
authors.initials: K
authors.lastname: Vivek
authors.forename: Robert R
authors.initials: RR
authors.lastname: Redfield
authors.forename: Thi-Sau
authors.initials: TS
authors.lastname: Migone
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.forename: Hooman
authors.initials: H
authors.lastname: Noorchashm