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Regulatory B cells in autoimmunity: developments and controversies

Nature Reviews Rheumatology volume 6, pages 636–643 (2010)Cite this article

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Abstract

Over a decade has now passed since the concept of B cells with a regulatory function was resurrected—B cells that produce antibodies with a suppressive effect were first reported in the 1960s and suppressor B cells in the 2000s. In the meantime, some aspects of regulatory B (BREG)-cell biology have been elucidated. Not only have scientists begun to unravel the mechanism of how BREG cells suppress immune responses and which cells they target, but their ontogeny and development has also begun to be determined. To date, key roles for BREG cells have been identified in the regulation of several immune-mediated processes, including autoimmunity and responses to infectious disease and cancer. This Review highlights these advances in the study of BREG cells, and outlines what is known about their phenotype as well as their suppressive role in autoimmunity from studies in both mice and humans. A particular emphasis is placed on BREG-cell function in rheumatic diseases.

Key Points

  • Regulatory B (BREG) cells potently suppress type I T-helper (TH1)-cell differentiation, inhibit autoimmune pathogenesis, restore immune homeostasis and repress antitumor immune responses (to promote cancer growth)

  • BREG cells suppress TH1-cell differentiation by the provision of interleukin (IL)-10 and via cell–cell contact

  • No definitive phenotype has been identified for BREG cells

  • Human BREG cells share several similarities with their rodent counterparts, including an immature phenotype and the capacity to suppress TH1-cell differentiation via the release of IL-10

  • Further studies on the ontogeny, phenotype and suppressive function of BREG cells are needed to understand their biology and function in the pathophysiology of autoimmune diseases, allergy, infection and cancer

  • Given the success in expanding BREG cells in vitro, BREG-cell-based therapy is a promising therapeutic avenue that could be useful in a wide range of immune diseases

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Figure 1: Distinguishing markers of distinct BREG-cell subsets.
Figure 2: Generation and mechanisms of action of BREG cells.

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Acknowledgements

C. Mauri's work is funded by grant MP/17707 from Arthritis Research UK (formerly the Arthritis Research Campaign) Program. P. A. Blair has been supported by the Oliver Bird Rheumatism Program and by grant P7575 from Lupus UK. He is currently funded by grant R080521 from Guy's and St Thomas Trust (awarded to G. Lombardi, Medical Research Council Centre for Transplantation, Kings College London).

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Authors and Affiliations

  1. Department of Medicine, Centre for Rheumatology Research, University College London, 46 Cleveland Street, London, W1T 4JF, UK

    Claudia Mauri

  2. Department of Nephrology and Transplantation, Medical Research Council Centre for Transplantation, 5th Floor Bermondsey Wing, Guy's Hospital, Kings College London, Great Maze Pond, London, SE1 9RT, UK

    Paul A. Blair

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C. Mauri and P. A. Blair contributed equally to all aspects of this manuscript.

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Correspondence to Claudia Mauri.

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Mauri, C., Blair, P. Regulatory B cells in autoimmunity: developments and controversies. Nat Rev Rheumatol 6, 636–643 (2010). https://doi.org/10.1038/nrrheum.2010.140

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