Transplantation tolerance modifies donor-specific B cell fate to suppress de novo alloreactive B cells
- 30 June 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 130 (7), 3453-3466
- https://doi.org/10.1172/JCI132814
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.Funding Information
- National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (1R01AI110513,P01AI097113)
This publication has 53 references indexed in Scilit:
- Antibody-Mediated Rejection of Solid-Organ AllograftsThe New England Journal of Medicine, 2018
- Long-Term Results in Recipients of Combined HLA-Mismatched Kidney and Bone Marrow Transplantation Without Maintenance ImmunosuppressionAmerican Journal of Transplantation, 2014
- Reversing Endogenous Alloreactive B Cell GC Responses With Anti-CD154 or CTLA-4IgAmerican Journal of Transplantation, 2013
- Acquisition of Humoral Transplantation Tolerance upon De Novo Emergence of B LymphocytesThe Journal of Immunology, 2011
- Tracking epitope-specific T cellsNature Protocols, 2009
- Memory Alloreactive B Cells and Alloantibodies Prevent Anti-CD154-Mediated Allograft AcceptanceThe Journal of Immunology, 2009
- Long-Term Control of Alloreactive B Cell Responses by the Suppression of T Cell HelpThe Journal of Immunology, 2008
- Naive CD4+ T Cell Frequency Varies for Different Epitopes and Predicts Repertoire Diversity and Response MagnitudeImmunity, 2007
- Peripheral deletion of mature alloreactive B cells induced by costimulation blockadeProceedings of the National Academy of Sciences of the United States of America, 2007
- Different sensitivity to receptor editing of B cells from mice hemizygous or homozygous for targeted Ig transgenesProceedings of the National Academy of Sciences of the United States of America, 2000