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

J Clin Invest. 2020 Jul 1;130(7):3453-3466. doi: 10.1172/JCI132814.


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.

Keywords: Antigen presenting cells; B cells; Immunology; Transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Female
  • Germinal Center / immunology*
  • Germinal Center / pathology
  • Isoantibodies / immunology*
  • Isoantigens / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / pathology
  • Transplantation Tolerance*


  • Isoantibodies
  • Isoantigens