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Checkpoints in lymphocyte development and autoimmune disease

Nature Immunology volume 11, pages 14–20 (2010)Cite this article

Abstract

Antigen receptor–controlled checkpoints in B lymphocyte development are crucial for the prevention of autoimmune diseases such as systemic lupus erythematosus. Checkpoints at the stage of pre–B cell receptor (pre-BCR) and BCR expression can eliminate certain autoreactive BCRs either by deletion of or anergy induction in cells expressing autoreactive BCRs or by receptor editing. For T cells, the picture is more complex because there are regulatory T (Treg) cells that mediate dominant tolerance, which differs from the recessive tolerance mediated by deletion and anergy. Negative selection of thymocytes may be as essential as Treg cell generation in preventing autoimmune diseases such as type 1 diabetes, but supporting evidence is scarce. Here we discuss several scenarios in which failures at developmental checkpoints result in autoimmunity.

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Figure 1: Pre-BCR cross-linking.
Figure 2: Model of involvement of complement and natural serum IgM in B cell central tolerance.
Figure 3: Weak epitopes fail to negatively select thymocytes.

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Acknowledgements

Supported by the Deutsche Forschungsgesellschaft (Koselleck grant P.S.ME 2764/1-1 to F.M.) and the US National Institutes of Health (ROI AI 045846, R37 AI 053102, ROI AI 051378 and POI CA 10990 to H.v.B.).

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  1. Harvard Medical School and Dana Farber Cancer Institute, Boston, Massachusetts, USA

    Harald von Boehmer

  2. Max Planck Institute for Infection Biology, Campus Charite, Berlin, Germany

    Fritz Melchers

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  1. Harald von Boehmer
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Correspondence to Harald von Boehmer or Fritz Melchers.

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Competing interests

F.M. is cofounder and member of the board of directors of 4-Antibody AG, Basel, Switzerland, a biotechnology company that generates and improves human monoclonal antibodies.

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von Boehmer, H., Melchers, F. Checkpoints in lymphocyte development and autoimmune disease. Nat Immunol 11, 14–20 (2010). https://doi.org/10.1038/ni.1794

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