Regulatory B Cells


B cells are best known for their ability to produce antibodies and instigate immune memory necessary for the protection of the host against foreign stimuli. However, certain subsets of B cells are increasingly shown to be capable of negative immune regulation by counteracting inflammation and suppressing the immune response. These cells are aptly termed ‘regulatory B cells’ or ‘Bregs’ and carry out their function by multiple mechanisms that include production of anti‐inflammatory cytokines and cognate interaction with other immune cells. Bregs are able to restore an immune response to homeostatic levels and as such play crucial roles in health conditions requiring suppression of inflammation and/or maintenance of tolerance such as in autoimmunity, graft tolerance, allergy, infection, cancer and pregnancy. Understanding how these potent and dynamic cells can be controlled in various immune situations offers a promising avenue for the development of novel prophylactic and immune therapy treatments.

Key Concepts

  • Regulatory B cells or Bregs are B‐cell subsets capable of downmodulating the immune response.
  • Bregs can suppress the immune response by producing anti‐inflammatory cytokines such as IL‐10 and TGF‐β, or through cell–cell contact with other immune cells.
  • Bregs can limit the severity and progression of autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis by recruiting regulatory T cells and inhibiting proinflammatory cytokine production by helper T cells.
  • Higher Breg frequency in peripheral circulation is correlated with operational tolerance in transplantation patients.
  • Bregs induce and promote allergen tolerance primarily through IL‐10 production.
  • Bregs can inhibit the immune response to viral, bacterial and parasitic infections, thereby allowing pathogen survival and disease progression.
  • Bregs in tumour sites can hinder effector immune cells from attacking and eliminating cancer cells.
  • In pregnancy, Bregs are likely to play an important role in the induction of maternal tolerance necessary for the successful growth of semiallogeneic foetus.

Keywords: regulatory B cells; immune suppression; tolerance; autoimmunity; cancer; infection; allergy; pregnancy; immune therapy

Figure 1. Mechanisms of Breg suppression. Bregs inhibit Th1 and Th17 responses, inducing a Th2‐like bias to the T‐cell response; Bregs also inhibit cytotoxic CD8+ T cells, curtail effector CD4+ T‐cell proliferation, and abrogate the proinflammatory cytokine response, pushing instead the differentiation of CD4+ T cells into Tregs and Tr1s (left panel). Bregs likewise affect other immune cells such as monocytes, dendritic cells and natural killer cells (right panel).


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Further Reading

Guzman‐Genuino RM and Diener KR (2017) Regulatory B cells in pregnancy: lessons from autoimmunity, graft tolerance, and cancer. Frontiers in Immunology 8: 172.

Mauri C and Menon M (2017) Human regulatory B cells in health and disease: therapeutic potential. Journal of Clinical Investigation 127 (3): 772–779.

Papp G, Boros P, Nakken B, et al. (2017) Regulatory immune cells and functions in autoimmunity and transplantation immunology. Autoimmunity Reviews 16 (5): 435–444.

Rosser EC and Mauri C (2015) Regulatory B cells: origin, phenotype, and function. Immunity 42 (4): 607–612.

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Guzman‐Genuino, Ruth Marian, and Diener, Kerrilyn R(Jan 2018) Regulatory B Cells. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026235]