title: Role of B lymphocytes in the pathogenesis of type 1 diabetes.
abstract: Though type 1 diabetes (T1D) is considered a T cell-mediated autoimmune disorder, recent evidence indicates that B cells play a critical role in disease. This conclusion is based in part on the success of anti-CD20 (rituximab) therapy, which by broadly depleting B cells delays disease progression in non-obese diabetic (NOD) mice and new-onset patients. B cell receptor (BCR) specificity to islet autoantigen is key. NOD mice whose B cell repertoire is biased toward insulin reactivity show increased disease development, while bias away from insulin reactivity largely prevents disease. Although the operative disease-promoting B cell effector function remains undefined, islet-antigen reactive B cells function in antigen presentation to diabetogenic CD4 T cells. Other studies implicate B cells in antigen presentation to CD8 T cells. B cell participation in TID appears predicated on faulty B cell tolerance. Here, we review extant findings implicating B cells in T1D in mice and men.
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E 19th Avenue, P18-8100, Mail Stop 8333, RC1 N, Aurora, CO, 80045-2537, USA, rochelle.hinman@ucdenver.edu.
authors.forename: Rochelle M
authors.initials: RM
authors.lastname: Hinman
authors.forename: John C
authors.initials: JC
authors.lastname: Cambier
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D018450:Disease Progression; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007155:Immunologic Factors / Q000494:pharmacology; D008212:Lymphocyte Depletion; D051379:Mice; D016688:Mice, Inbred NOD; D058990:Molecular Targeted Therapy; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000276:immunology*; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; D011947:Receptors, Antigen, B-Cell; D000069283:Rituximab