title: Transplantation tolerance: don't forget about the B cells.
abstract: Establishing a state of transplantation tolerance that leads to indefinite graft survival without the need for lifelong immunosuppression has been achieved successfully in limited numbers of transplant recipients in the clinic. These successes led to studies aimed at identifying potential biomarkers that diagnose allograft tolerance and identify the patients most amenable to drug minimization, and implicated an enriched B cell signature of tolerance. The emergence of a specialized subset of regulatory B cell (Bregs), that possess immune-modulatory function in inflammation and autoimmune disease, raised the possibility that Bregsplay critical roles in the promotion of transplantation tolerance and that Bregsare the underlying explanation for the B cell signature of tolerance. However, B cells are best known to play a key role in humoral immunity, and excessive production of donor specific antibodies has clear deleterious effects in transplantation. Thus, for tolerance to be persistent, alloantibody responses must also be curtailed, either through the suppression of T cell help or the induction of B cell-intrinsic dysfunction. Recent findings indicate a unique subset of follicular regulatory T cells (Tfr) that can suppress B cell function and induce epigenetic modifications that result in sustained defects in B cell differentiation and function. In this review, we summarize studies in animals and humans that suggest roles for Bregsand dysfunctional B cells in transplantation tolerance, and discuss how these insights may provide a roadmap for new approaches to diagnose, and new therapies to induce allograft tolerance.
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL, USA.
authors.forename: A S
authors.identifier: 0000-0003-0460-0196
authors.initials: AS
authors.lastname: Chong
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Khiew
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D015415:Biomarkers; D017635:Clonal Anergy; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D016753:Interleukin-10 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D023001:Transplantation Tolerance
chemical_list: D015415:Biomarkers; D016753:Interleukin-10
keywords: Bregs; IL-10; anergy; biomarkers; transplantation tolerance