title: Checkpoints in lymphocyte development and autoimmune disease.
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 (T(reg)) 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 T(reg) 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.
authors.affiliation: Harvard Medical School and Dana Farber Cancer Institute, Boston, Massachusetts, USA. harald_von_boehmer@dfci.harvard.edu
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
authors.forename: Fritz
authors.initials: F
authors.lastname: Melchers
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D018448:Models, Immunological; D054420:Pre-B Cell Receptors / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D054420:Pre-B Cell Receptors