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

23 Scopus citations

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Parsons, R. F., Vivek, K., Rostami, S. Y., Zekavat, G., Ziaie, S. M., Luo, Y., Koeberlein, B., Redfield, R. R., Cancro, M. P., Naji, A., & 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