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B cells with immune-regulating function in transplantation

Nature Reviews Nephrology volume 10, pages 389–397 (2014)Cite this article

Subjects

Key Points

  • Various populations of B cells with immune-regulatory functions exist in mice and humans

  • Regulatory B (BREG) cells can control immune responses via diverse mechanisms, including cytokines, growth factors and cell–cell interactions

  • Immunosuppression-free renal transplant recipients have an altered B-cell compartment compared with patients on immunosuppression who have stable graft function, suggesting that B cells have a crucial role in immune-system regulation

  • BREG cells have therapeutic potential in animal models of transplantation

  • More investigation is required to elucidate the exact role of B cells in transplant tolerance and to develop strategies to expand BREG cell populations

Abstract

In transplantation, the contribution of B cells to the rejection or acceptance of the allograft is a topic of major interest. The presence of donor-specific antibodies in transplant recipients is often associated with decreased graft function and rejection, clearly indicating a pathogenetic role of B cells in transplantation. However, data from studies in humans and rodents suggest that under certain conditions, B cells have the capacity to control or regulate the immune response to a transplanted organ. Although a great deal of attention has been focused on B cells in human and murine models of autoimmunity, our understanding of the role of these cells in transplantation is limited at present. Indeed, results in this setting are controversial and seem to depend on the model system used or the clinical situation studied. Here, we review the current understanding of the various phenotypes and roles that have been associated with immune-regulating B cells. We also discuss the mechanisms employed by subsets of these regulatory B cells to control the immune response in transplant recipients and in animal models of transplantation.

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Figure 1: B cell development and tolerance within the bone marrow.
Figure 2: Phenotypes of BREG cells.
Figure 3: Mechanisms of action of BREG cells.

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Acknowledgements

The authors' work is funded by grants from the Wellcome Trust, UK Medical Research Council, British Heart Foundation and European Union through the ONE Study, Translating Research into Action for Diabetes (TRIAD) and Biomarker Driven Personal Immunosuppression (Bio-DRIM) projects, and the Immune Tolerance Network.

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  1. Nuffield Department of Surgical Sciences, Transplantation Research Immunology Group, University of Oxford John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Jessica Stolp & Kathryn J. Wood

  2. Transplantation Biology Research Centre, Massachusetts General Hospital, Room 5102, Charlestown, 02129, MA, USA

    Laurence A. Turka

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J.S. researched the data for the article. J.S. and K.J.W. provided substantial contributions to discussions of the article content and wrote the manuscript. All authors undertook review and/or editing of the manuscript before submission.

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Correspondence to Kathryn J. Wood.

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J.S. and K.J.W. declare no competing interests. L.A.T. has a spouse employed by, and owns equity in, Novartis.

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Stolp, J., Turka, L. & Wood, K. B cells with immune-regulating function in transplantation. Nat Rev Nephrol 10, 389–397 (2014). https://doi.org/10.1038/nrneph.2014.80

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