title: Altered B cell signalling in autoimmunity.
abstract: Recent work has provided new insights into how altered B cell-intrinsic signals - through the B cell receptor (BCR) and key co-receptors - function together to promote the pathogenesis of autoimmunity. These combined signals affect B cells at two distinct stages: first, in the selection of the naive repertoire; and second, during extrafollicular or germinal centre activation responses. Thus, dysregulated signalling can lead to both an altered naive BCR repertoire and the generation of autoantibody-producing B cells. Strikingly, high-affinity autoantibodies predate and predict disease in several autoimmune disorders, including type 1 diabetes and systemic lupus erythematosus. This Review summarizes how, rather than being a downstream consequence of autoreactive T cell activation, dysregulated B cell signalling can function as a primary driver of many human autoimmune diseases.
authors.affiliation: Seattle Children's Research Institute, 1900 9th Avenue, Seattle, Washington 98101, USA.|Department of Immunology, University of Washington School of Medicine.|Department of Pediatrics, University of Washington School of Medicine, 750 Republican Street, Seattle, Washington 98109, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Rawlings
authors.affiliation: Seattle Children's Research Institute, 1900 9th Avenue, Seattle, Washington 98101, USA.|Department of Immunology, University of Washington School of Medicine.
authors.forename: Genita
authors.initials: G
authors.lastname: Metzler
authors.affiliation: Seattle Children's Research Institute, 1900 9th Avenue, Seattle, Washington 98101, USA.|Department of Immunology, University of Washington School of Medicine.
authors.forename: Michelle
authors.initials: M
authors.lastname: Wray-Dutra
authors.affiliation: Seattle Children's Research Institute, 1900 9th Avenue, Seattle, Washington 98101, USA.|Department of Pediatrics, University of Washington School of Medicine, 750 Republican Street, Seattle, Washington 98109, USA.
authors.forename: Shaun W
authors.initials: SW
authors.lastname: Jackson
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011947:Receptors, Antigen, B-Cell