Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes

Ronald F. Parsons, Kumar Vivek, Susan Y. Rostami, Ghazal Zekavat, Seyed M. Ziaie, Yanping Luo, Brigitte Koeberlein, Robert R. Redfield, Michael P. Cancro, Ali Naji, Hooman Noorchashm

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)614-620
Number of pages7
JournalJournal of Immunology
Volume186
Issue number1
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

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Transplantation Tolerance
B-Lymphocytes
Allografts
Isoantibodies
Isoantigens
T-Lymphocytes
Clonal Deletion
Lymphocytes
Self Tolerance
B-Lymphoid Precursor Cells
Humoral Immunity
Transplantation
Transplants

ASJC Scopus subject areas

  • Immunology

Cite this

Parsons, R. F., Vivek, K., Rostami, S. Y., Zekavat, G., Ziaie, S. M., Luo, Y., ... Noorchashm, H. (2011). Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes. Journal of Immunology, 186(1), 614-620. https://doi.org/10.4049/jimmunol.1002873

Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes. / Parsons, Ronald F.; Vivek, Kumar; Rostami, Susan Y.; Zekavat, Ghazal; Ziaie, Seyed M.; Luo, Yanping; Koeberlein, Brigitte; Redfield, Robert R.; Cancro, Michael P.; Naji, Ali; Noorchashm, Hooman.

In: Journal of Immunology, Vol. 186, No. 1, 01.01.2011, p. 614-620.

Research output: Contribution to journalArticle

Parsons, RF, Vivek, K, Rostami, SY, Zekavat, G, Ziaie, SM, Luo, Y, Koeberlein, B, Redfield, RR, Cancro, MP, Naji, A & Noorchashm, H 2011, 'Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes', Journal of Immunology, vol. 186, no. 1, pp. 614-620. https://doi.org/10.4049/jimmunol.1002873
Parsons, Ronald F. ; Vivek, Kumar ; Rostami, Susan Y. ; Zekavat, Ghazal ; Ziaie, Seyed M. ; Luo, Yanping ; Koeberlein, Brigitte ; Redfield, Robert R. ; Cancro, Michael P. ; Naji, Ali ; Noorchashm, Hooman. / Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes. In: Journal of Immunology. 2011 ; Vol. 186, No. 1. pp. 614-620.
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