title: Regulation of autoreactive B cells: checkpoints and activation.
abstract: It has become clear that the autoreactive B cells are a part of the normal naïve 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 naïve 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.
authors.affiliation: Tumor Immunobiology Program, Department of Medicine, James Graham Brown Cancer Center, Delia D. Baxter Research Building, Room 119A, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
authors.forename: Chuanlin
authors.initials: C
authors.lastname: Ding
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D001324:Autoantigens; D051193:Toll-Like Receptors