title: B cell tolerance and positive selection in lupus.
abstract: Systemic lupus erythematosus is considered a prototype of systemic autoimmune diseases; however, despite considerable advances in recent years in the understanding of basic mechanisms in immunology, little progress has been made in elucidating the etiology and pathogenesis of this disease. This even holds for inbred mice, such as the lupus-prone New Zealand Black/New Zealand White F(1) mice, which are all genetically programmed to develop lupus at a predetermined age. This frustrating state of affairs calls for a fundamental change in our scientific thinking and the opening of new directions in lupus research. In this study, we suggest that intrinsic B cell tolerance mechanisms are not grossly impaired in lupus-prone mice, but that an unusually strong positive selection event recruits a small number of autoreactive B cells to the germinal centers. This event could be facilitated by nucleic acid-protein complexes that are created by somatic changes in the susceptible animal.
authors: Department of Medicine, Hadassah University Hospital, Hebrew University Faculty of Medicine, Jerusalem, Israel.
authors: Dan
authors: D
authors: Eilat
authors: Matthias
authors: M
authors: Wabl
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008814:Mice, Inbred NZB