title: B cells take the front seat: dysregulated B cell signals orchestrate loss of tolerance and autoantibody production.
abstract: A significant proportion of autoimmune-associated genetic variants are expressed in B cells, suggesting that B cells may play multiple roles in autoimmune pathogenesis. In this review, we highlight recent studies demonstrating that even modest alterations in B cell signaling are sufficient to promote autoimmunity. First, we describe several examples of genetic variations promoting B cell-intrinsic initiation of autoimmune germinal centers and autoantibody production. We highlight how dual antigen receptor/toll-like receptor signals greatly facilitate this process and how activated, self-reactive B cells may function as antigen presenting cells, leading to loss of T cell tolerance. Further, we propose that B cell-derived cytokines may initiate and/or sustain autoimmune germinal centers, likely also contributing, in parallel, to programing of self-reactive T cells.
authors: Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States; Seattle Children's Research Institute, Seattle, WA, United States.
authors: Shaun W
authors: SW
authors: Jackson
authors: Department of Immunology, University of Washington School of Medicine, Seattle, WA, United States; Seattle Children's Research Institute, Seattle, WA, United States.
authors: Nikita S
authors: NS
authors: Kolhatkar
authors: Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States; Department of Immunology, University of Washington School of Medicine, Seattle, WA, United States; Seattle Children's Research Institute, Seattle, WA, United States. Electronic address: drawling@u.washington.edu.
authors: David J
authors: DJ
authors: Rawlings
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D015398:Signal Transduction
chemical_list: D001323:Autoantibodies; D016207:Cytokines