1. Acquisition of Humoral Transplantation Tolerance upon De Novo Emergence of B Lymphocytes.
- Author
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Parsons, Ronald F., Vivek, Kumar, Rostami, Susan Y., Zekavat, Ghazal, Ziaie, Seyed M., Yanping Luo, Koeberlein, Brigitte, Redfield, Robert R., Cancro, Michael P., Naji, Ali, and Noorchashm, Hooman
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TRANSPLANTATION of organs, tissues, etc. , *ANTIGENS , *B cells , *T cells , *LABORATORY mice , *HOMOGRAFTS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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