title: The ups and downs of negative (and positive) selection of B cells.
abstract: Central and peripheral tolerance checkpoints are in place to remove autoreactive B cell populations and prevent the development of autoimmunity. In this issue of the JCI, Pala and colleagues reveal that individuals with the X-linked immunodeficiency Wiskott-Aldrich syndrome (WAS) have opposite alterations at central and peripheral B cell checkpoints: a more stringent selection for central tolerance, resulting in reduced numbers of autoreactive cells at the emergent immature B cell stage, and a relaxed selection for peripheral tolerance, resulting in an increased frequency of autoreactive cells in the mature naive B cell compartment. Moreover, reinstatement of the WAS gene in these patients restored both B cell tolerance checkpoints. These results suggest that, in a normal situation, mature naive B cells undergo a positive selection step driven by self-antigens, kept in control by Tregs.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Weill
authors.forename: Claude-Agnès
authors.initials: CA
authors.lastname: Reynaud
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D014923:Wiskott-Aldrich Syndrome / Q000628:therapy*; D051316:Wiskott-Aldrich Syndrome Protein / Q000627:therapeutic use*
chemical_list: D051316:Wiskott-Aldrich Syndrome Protein