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

Stella H.W. 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 journalArticlepeer-review

5 Scopus citations


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
JournalJournal of Clinical Investigation
Issue number7
StatePublished - Jul 1 2020

ASJC Scopus subject areas

  • Medicine(all)


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