TY - JOUR
T1 - Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes
AU - Parsons, Ronald F.
AU - Vivek, Kumar
AU - Rostami, Susan Y.
AU - Zekavat, Ghazal
AU - Ziaie, Seyed M.
AU - Luo, Yanping
AU - Koeberlein, Brigitte
AU - Redfield, Robert R.
AU - Cancro, Michael P.
AU - Naji, Ali
AU - Noorchashm, Hooman
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/1/1
Y1 - 2011/1/1
N2 - A major obstacle to transplantation tolerance is humoral immunity. In this paper, we demonstrate that the intrinsic developmental propensity of the B lymphocyte compartment for acquisition of self-tolerance can be harnessed to induce humoral unresponsiveness to transplanted alloantigens. In the current study, when transitional B cells developed in the presence of donor lymphoid cells, the mature B lymphocyte compartment failed to mount a donor-specific alloantibody response to an organ transplant - despite unrestrained acute T cell-mediated allograft rejection. Specifically, we generated an experimental system wherein a B6 strain B cell compartment developed de novo in the presence of F1 (B6xBALB/c) lymphoid cells and in a T cell-deficient setting. Following establishment of a steady-state B cell compartment, these B6 mice were transplanted with heterotopic cardiac allografts from allogeneic BALB/c donors. The mice were then inoculated with purified syngeneic B6 T cells. As expected, all cardiac allografts were acutely rejected. However, the B lymphocyte compartment of these mice was completely inert in its capacity to form a BALB/c-specific alloantibody response. Using an alloantigen-specific Ig transgenic system, we demonstrated that this profound degree of humoral tolerance was caused by clonal deletion of alloreactive specificities from the primary B cell repertoire. Thus, de novo B cell compartment development at the time of transplantation is of critical importance in recipient repertoire "remodeling" to a humoral tolerant state.
AB - A major obstacle to transplantation tolerance is humoral immunity. In this paper, we demonstrate that the intrinsic developmental propensity of the B lymphocyte compartment for acquisition of self-tolerance can be harnessed to induce humoral unresponsiveness to transplanted alloantigens. In the current study, when transitional B cells developed in the presence of donor lymphoid cells, the mature B lymphocyte compartment failed to mount a donor-specific alloantibody response to an organ transplant - despite unrestrained acute T cell-mediated allograft rejection. Specifically, we generated an experimental system wherein a B6 strain B cell compartment developed de novo in the presence of F1 (B6xBALB/c) lymphoid cells and in a T cell-deficient setting. Following establishment of a steady-state B cell compartment, these B6 mice were transplanted with heterotopic cardiac allografts from allogeneic BALB/c donors. The mice were then inoculated with purified syngeneic B6 T cells. As expected, all cardiac allografts were acutely rejected. However, the B lymphocyte compartment of these mice was completely inert in its capacity to form a BALB/c-specific alloantibody response. Using an alloantigen-specific Ig transgenic system, we demonstrated that this profound degree of humoral tolerance was caused by clonal deletion of alloreactive specificities from the primary B cell repertoire. Thus, de novo B cell compartment development at the time of transplantation is of critical importance in recipient repertoire "remodeling" to a humoral tolerant state.
UR - http://www.scopus.com/inward/record.url?scp=79251561881&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79251561881&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1002873
DO - 10.4049/jimmunol.1002873
M3 - Article
C2 - 21084661
AN - SCOPUS:79251561881
SN - 0022-1767
VL - 186
SP - 614
EP - 620
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -