B cells regulate autoimmunity by provision of IL-10

Abstract

To assess the importance of B cell control of T cell differentiation, we analyzed the course of the T helper type 1 (TH1)-driven disease experimental autoimmune encephalomyelitis in mice with an altered B cell compartment. We found that recovery was dependent on the presence of autoantigen-reactive B cells. B cells from recovered mice produced interleukin 10 (IL-10) in response to autoantigen. With a bone marrow chimeric system, we generated mice in which IL-10 deficiency was restricted to B cells but not T cells. In the absence of IL-10 production by B cells, the pro-inflammatory type 1 immune response persisted and mice did not recover. These data show that B cell–derived IL-10 plays a key role in controlling autoimmunity.

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Figure 1: Severe EAE in B cell–deficient mice correlates with uncontrolled type 1 autoreactivity.
Figure 2: B cells from recovered B6 mice produce MOG-specific IL-10.
Figure 3: B cell production of IL-10 is required for recovery from EAE.
Figure 4: Further analysis of the requirement for B cells in EAE recovery.
Figure 5: B cell IL-10 deficiency correlates with enhanced type 1 autoreactivity.
Figure 6: IL-10–producing B cells can transfer recovery from EAE.

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Acknowledgements

Supported by grants from the Medical Research Council UK and the Wellcome Trust and by the Wellcome Trust (D.G.) and Medical Research Council (S. M. A).

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Correspondence to Stephen M. Anderton.

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Fillatreau, S., Sweenie, C., McGeachy, M. et al. B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3, 944–950 (2002). https://doi.org/10.1038/ni833

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