title: Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases.
abstract: B-cell depletion therapy has beneficial effects in autoimmune diseases. This is only partly explained by an elimination of autoantibodies. How does B-cell depletion improve disease? Here, we review preclinical studies showing that B cells can propagate autoimmune disorders through cytokine production. We also highlight clinical observations indicating the relevance of these B-cell functions in human autoimmunity. Abnormalities in B-cell cytokine production have been observed in rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and systemic lupus erythematosus. In the first two diseases, B-cell depletion erases these abnormalities, and improves disease progression, suggesting a causative role for defective B-cell cytokine expression in disease pathogenesis. However, in the last two disorders, the pathogenic role of B cells and the effect of B-cell depletion on cytokine-producing B cells remain to be clarified. A better characterization of cytokine-expressing human B-cell subsets, and their modulation by B cell-targeted therapies might help understanding both the successes and failures of current B cell-targeted approaches. This may even lead to the development of novel strategies to deplete or amplify selectively pathogenic or protective subsets, respectively, which might be more effective than global depletion of the B-cell compartment.
authors.affiliation: Deutsches Rheuma-Forschungszentrum, A Leibniz Institute, Berlin, Germany.
authors.forename: Andreia C
authors.initials: AC
authors.lastname: Lino
authors.affiliation: Deutsches Rheuma-Forschungszentrum, A Leibniz Institute, Berlin, Germany.|CC12, Department of Medicine/Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University, 3801 University, Montreal, QC, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: Deutsches Rheuma-Forschungszentrum, A Leibniz Institute, Berlin, Germany.|Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, Paris, France.|Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants Malades, Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Fillatreau
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D058990:Molecular Targeted Therapy; D057170:Translational Research, Biomedical
chemical_list: D016207:Cytokines
keywords: B cells; autoimmunity; cytokine; multiple sclerosis; rheumatoid arthritis