Transplantation tolerance: don't forget about the B cells. (28th February 2017)

• Record Type: Journal Article
• Authors: Chong, A. S.; Khiew, S. H.
• Is Part Of: Clinical and experimental immunology. Volume 189:Number 2(2017:Aug.)
• Page Start: 171
• Page End: 180
• Publication Date: 2017-02-28
• Subjects: anergy -- Bregs -- biomarkers -- IL‐10 -- transplantation tolerance; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12927
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: 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 Bregs play critical roles in the promotion of transplantation tolerance and that Bregs are 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 Bregs and 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. Abstract : In this review, Chong and Khiew summarize studies in animals and humans that suggest roles for Bregs and dysfunctional B cells in allograft tolerance. They also discuss how these insights may provide a roadmap for new approaches for diagnosing transplantation tolerance and for developing new therapies to improve long‐term graft outcomes though the induction of transplantation tolerance.