title: B cells and immunological tolerance.
abstract: Work from multiple groups continues to provide additional evidence for the powerful and highly diverse roles, both protective and pathogenic, that B cells play in autoimmune diseases. Similarly, it has become abundantly clear that antibody-independent functions may account for the opposing influences that B cells exercise over other arms of the immune response and ultimately over autoimmunity itself. Finally, it is becoming apparent that the clinical impact of B-cell depletion therapy may be, to a large extent, determined by the functional balance between different B-cell subsets that may be generated by this therapeutic intervention. In this review, we postulate that our perspective of B-cell tolerance and our experimental approach to its understanding are fundamentally changed by this view of B cells. Accordingly, we first discuss current knowledge of B-cell tolerance conventionally defined as the censoring of autoantibody-producing B cells (with an emphasis on human B cells). Therefore, we discuss a different model that contemplates B cells not only as targets of tolerance but also as mediators of tolerance. This model is based on the notion that the onset of clinical autoimmune disease may require a B-cell gain-of-pathogenic function (or a B-cell loss-of-regulatory-function) and that accordingly, disease remission may depend on the restoration of the physiological balance between B-cell pathogenic and protective functions.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: Nataly
authors.initials: N
authors.lastname: Manjarrez-Orduño
authors.forename: Tâm D
authors.initials: TD
authors.lastname: Quách
authors.forename: Iñaki
authors.initials: I
authors.lastname: Sanz
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*