title: The BAFF/APRIL system: an important player in systemic rheumatic diseases.
abstract: Many rheumatic diseases have an autoimmune basis, characterized by organ-specific inflammation and tissue destruction. Diseases such as rheumatoid arthritis, systemic lupus erythematosus or Sjögren's syndrome often associate with abnormal B cell function and the production of various autoantibodies. B cell activating factor belonging to the TNF family (BAFF) is a B cell survival factor essential for B cell maturation, but also contributes to autoimmunity when overexpressed in mice. In addition, elevated levels of BAFF have been detected in the serum of patients with various rheumatic diseases, suggesting a role for this factor in these pathologies. BAFF has additional functions that may be important in rheumatic diseases. For instance, excess BAFF leads to the expansion of a subset of B cells named marginal zone (MZ) B cells, a cell type able to activate naïve T cells. In addition, expansion of the MZ B cell population correlates with certain autoimmune diseases, and these cells have been detected in inflamed tissues in mice and humans. Recently, BAFF was shown to also stimulate T cell activation, an aspect that may also contribute to autoimmunity. Finally, BAFF has emerged as a potent survival factor for B cell lymphomas and as such may be involved in promoting B cell cancers. This result possibly offers an explanation for the occasional lymphoma complication observed in a subset of patients with certain rheumatic diseases, particularly Sjögren's syndrome. New elements about BAFF biology indicate that this factor may be involved in a wider range of pathologies than first anticipated, and inhibitors of this factor are likely to provide attractive new treatments for rheumatic diseases and B cell lymphomas.
authors.affiliation: The Garvan Institute of Medical Research, Department of Arthritis and Inflammation, Darlinghurst, Australia. f.mackay@garvan.org.au
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.forename: Frederic
authors.initials: F
authors.lastname: Sierro
authors.forename: Shane T
authors.initials: ST
authors.lastname: Grey
authors.forename: Tom P
authors.initials: TP
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D015448:Leukemia, B-Cell / Q000276:immunology; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D009374:Neoplasms, Experimental / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D012216:Rheumatic Diseases / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D012859:Sjogren's Syndrome / Q000276:immunology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D008024:Ligands; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C435926:TNFRSF13C protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; C486662:Tnfrsf13c protein, mouse; C491959:Tnfsf13 protein, mouse; C505720:Tnfsf13b protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha