B-cell tolerance in transplantation: is repertoire remodeling the answer?
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.
Parsons
Ronald F
RF
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.
Vivek
Kumar
K
Redfield
Robert R
RR
Migone
Thi-Sau
TS
Cancro
Michael P
MP
Naji
Ali
A
Noorchashm
Hooman
H