Transplantation tolerance modifies donor-specific B cell fate to suppress de novo alloreactive B cells

Stella Hw Khiew, Dharmendra Jain, Jianjun Chen, Jinghui Yang, Dengping Yin, James S. Young, Alexander Dent, Roger Sciammas, Maria Luisa Alegre, Anita S. Chong

Research output: Contribution to journalArticle

Abstract

The absence of alloantibodies is a feature of transplantation tolerance. Although the lack of T cell help has been evoked to explain this absence, herein we provide evidence for B cell-intrinsic tolerance mechanisms. Using a murine model of heart tolerance, we showed that alloreactive B cells were not deleted but rapidly lost their ability to differentiate into germinal center B cells and secrete donor-specific antibodies. We inferred that tolerant alloreactive B cells retained their ability to sense alloantigen because they continued to drive T cell maturation into CXCR5+PD-1+ T follicular helper cells. Unexpectedly, dysfunctional alloreactive B cells acquired the ability to inhibit antibody production by new naive B cells in an antigen-specific manner. Thus, tolerant alloreactive B cells contribute to transplantation tolerance by foregoing germinal center responses while retaining their ability to function as antigen-presenting cells and by actively suppressing de novo alloreactive B cell responses.

Original languageEnglish (US)
Pages (from-to)3453-3466
Number of pages14
JournalThe Journal of clinical investigation
Volume130
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • Antigen presenting cells
  • B cells
  • Immunology
  • Transplantation

ASJC Scopus subject areas

  • Medicine(all)

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    Khiew, S. H., Jain, D., Chen, J., Yang, J., Yin, D., Young, J. S., Dent, A., Sciammas, R., Alegre, M. L., & Chong, A. S. (2020). Transplantation tolerance modifies donor-specific B cell fate to suppress de novo alloreactive B cells. The Journal of clinical investigation, 130(7), 3453-3466. https://doi.org/10.1172/JCI132814