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2007 | 55 | 2 | 83-89
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Regulation of autoreactive B cells: checkpoints and activation

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It has become clear that the autoreactive B cells are a part of the normal na?ve B cell repertoire in the periphery, despite the fact that they undergo a series of checkpoints, which include receptor editing (revision), clonal deletion, and anergy. However, most of those B cells reactive against self antigen remain functionally na?ve for autoantibody production by differential peripheral checkpoints. Therefore, the presence of autoreactive B cells does not always signify disease. Regulation of their activation and effector functions will determine the ultimate outcome. Although autoreactive B cell tolerance is well maintained in the healthy individual, the existence of pathogenic autoantibodies in autoimmune diseases indicates that these tolerogenic checkpoints are broken. Recent studies have demonstrated that autoreactive B cells are regulated by a composite of factors, such as genetic susceptibility and environmental triggers such as bacterial and viral infections as well as other immune cells. Interestingly, Toll-like receptors, previously considered as pattern-recognition receptors to detect and sense pathogens, may also have a potential to recognize self antigens and regulate autoreactive B cells for activation. Understanding the mechanisms of autoreactive B cell regulation and activation may help in identifying novel targets for the treatment of autoimmune diseases.
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Jun Yan, Tumor Immunobiology Program, James Graham Brown Cancer Center, Delia D. Baxter Research Building, Room 119A, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA
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