B lymphocytes contribute to autoimmune disease pathogenesis: current trends and clinical implications.
Abnormal B lymphocytes influence the pathogenesis of many autoimmune diseases, in addition to serving as the origin of pathogenic autoantibodies. Although aberrant B cell function and autoimmunity have complex polygenic origins, recent studies in mouse models of autoimmune diseases have revealed overlapping defects in signal transduction pathways that alter B cell survival or activation, and lead to an autoimmune phenotype. Discovery of these important signaling pathways in mice has lead to an intense search for B cell abnormalities that correlate with autoimmune diseases in humans. This search has identified potential targets for therapeutic intervention that are the focus of planned and ongoing human clinical trials. This promises an arsenal of highly targeted, less toxic therapies focused on restoring normal B cell function that will eliminate pathogenic autoantibodies and replace the current use of immunosuppressive drugs.
Tuscano
Joseph M
JM
Department of Internal Medicine, University of California, Davis Medical Center, Sacramento, CA 95817, USA. joseph.tuscano@ucdmc.ucdavis.edu
Harris
Geoffrey S
GS
Tedder
Thomas F
TF
D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D015551:Autoimmunity; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D018448:Models, Immunological; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D018941:Antigens, CD19; D018951:Antigens, CD20; D053264:B-Cell Activating Factor; D019013:CD40 Antigens; D008565:Membrane Proteins; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha