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Not always the bad guys: B cells as regulators of autoimmune pathology

Nature Reviews Immunology volume 8, pages 391–397 (2008)Cite this article

Abstract

When B cells react aggressively against self, the potential for pathology is extreme. It is therefore not surprising that B-cell depletion is seen as an attractive therapy in autoimmune diseases. However, B cells can also be essential for restraining unwanted autoaggressive T-cell responses. Recent advances have pointed to interleukin-10 (IL-10) production as a key component in B-cell-mediated immune regulation. In this Opinion article, we develop a hypothesis that triggering of Toll-like receptors controls the propensity of B cells for IL-10 production and immune suppression. According to this model, B cells can translate exposure to certain microbial infections into protection from chronic inflammatory diseases.

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Figure 1: B-cell-derived interleukin-10: stimuli and effects.
Figure 2: A model for how selective Toll-like receptor triggering of B cells to produce interleukin-10 constrains the autoaggressive response in experimental autoimmune encephalomyelitis.

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Acknowledgements

Work in the authors' laboratories is supported by the Deutsche Forschungsgemeinschaft (SFB-650), the Association pour la Recherche sur la Sclérose En Plaques (ARSEP), and the Hertie Stiftung (S.F.); the Wellcome Trust (D.G.); and the Medical Research Council, the Wellcome Trust and the UK Multiple Sclerosis Society (S.M.A.). S.M.A. is an MRC Senior Research Fellow and holds a Research Councils UK Fellowship in Translational Medicine.

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Authors and Affiliations

  1. Simon Fillatreau is at the Immune regulation group, Deutsches Rheuma-ForschungsZentrum, Charitéplatz 1, 10117 Berlin, Germany.,

    Simon Fillatreau

  2. David Gray and Stephen M. Anderton are at the University of Edinburgh, Institute of Immunology and Infection Research, School of Biological Sciences, Kings Buildings, West Mains Road, Edinburgh EH9 3JT, UK.,

    David Gray

  3. Stephen M. Anderton is also at the University of Edinburgh, Centre for Inflammation Research, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.,

    Stephen M. Anderton

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Glossary

Anterior-chamber-associated immune deviation

(ACAID). Systemic antigen-specific tolerance that develops after inoculation of antigen into the immune-privileged site of the anterior chamber of the eye.

Collagen-induced arthritis

(CIA). An experimental model of rheumatoid arthritis. Arthritis is induced by immunization of susceptible animals with type II collagen.

Epitope spreading

A term originally applied to responses to autoantigens that tend to become more diverse as the response persists.

Experimental autoimmune encephalomyelitis

(EAE). An animal model of multiple sclerosis. EAE can be induced in several mammalian species by immunization with myelin-derived antigens together with adjuvant. The immunized animals develop a paralytic disease with inflammation and demyelination in the brain and spinal cord that has several pathological features in common with multiple sclerosis in humans.

Inflammatory bowel disease

(IBD). A chronic condition of the intestine that is characterized by severe inflammation and mucosal destruction. The commonest forms in humans are ulcerative colitis and Crohn's disease. Animal models indicate that they result from the dysregulation of the local immune response to normally harmless commensal bacteria.

Non-obese diabetic (NOD) mice

A mouse strain that has a polygenic susceptibility to spontaneous development of autoimmune, type 1 diabetes. The main component of susceptibility is the unique MHC haplotype H2g7.

T-cell receptor (TCR)-invariant T cells

A term to describe conserved subsets of T cells that express invariant TCR among which are the CD1d-restricted natural killer T cells expressing Vα14–Jα18, and the MR1-restricted mucosal associated invariant T (MAIT) cells expressing Vα19–Jα33.

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Fillatreau, S., Gray, D. & Anderton, S. Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol 8, 391–397 (2008). https://doi.org/10.1038/nri2315

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