title: Antigen-induced apoptotic death of Ly-1 B cells responsible for autoimmune disease in transgenic mice.
abstract: Studies on transgenic mice expressing immunoglobulins against self-antigens have shown that self-tolerance is maintained by active elimination (clonal deletion), functional inactivation (clonal anergy) of self-reactive B cells, or a combination of both. We have established and characterized a transgenic mouse line expressing an anti-erythrocyte autoantibody. In contrast to other autoantibody transgenic lines, about 50% of the animals of this transgenic line suffer from autoimmune disease, indicating a loss of self-tolerance. Here we show that peritoneal Ly-1 B cells (also known as B-1 cells) are responsible for this autoimmune disease in our transgenic mice. A few self-reactive Ly-1 B cells that have somehow escaped the deletion mechanism expand in the peritoneum because of the absence of self-antigen. These Ly-1 B cells are eliminated in vivo by apoptosis once exposed to self-antigen. On the basis of these results we propose a novel autoantibody production mechanism whereby self-reactive B cells sequestered in compartments free of self-antigens may survive, proliferate and be activated for generation of pathogenic autoantibodies in autoimmune diseases.
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Tsubata
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.forename: S
authors.initials: S
authors.lastname: Kumagai
authors.forename: H
authors.initials: H
authors.lastname: Imura
authors.forename: T
authors.initials: T
authors.lastname: Honjo
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000473:pathology* / Q000502:physiology*; D016923:Cell Death / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology
chemical_list: D001323:Autoantibodies