A transgenic model of autoimmune hemolytic anemia.
We made double transgenic mice bearing immunoglobulin heavy and light chain genes encoding an autoantibody against the mouse erythrocyte by the cross of C57BL/6 mice carrying the transgene for each chain of the immunoglobulin. Although no obvious disorders were found in the single-chain transgenic mice, severely anemic symptoms were found in some of the double transgenic mice, in which most B cells express, at least on their surface, the autoantibody reactive to self-antigens on the erythrocyte. Individual double-transgenic mice showed a wide variation of phenotypes between severe anemia and no symptoms. Both deletion and anergy of autoreactive B cells were seen in each individual mouse, but their relative contribution to self-tolerance was variable and not directly related to the severity of anemia or the amount of the autoantibody produced. This transgenic system provides a good autoimmune disease model for exploring its onset mechanism, and means of its treatment and prevention.
Okamoto
M
M
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
Murakami
M
M
Shimizu
A
A
Ozaki
S
S
Tsubata
T
T
Kumagai
S
S
Honjo
T
T
D000743:Anemia, Hemolytic / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D001323:Autoantibodies / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D003433:Crosses, Genetic; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005803:Genes, Immunoglobulin; D007074:Immunoglobulin G / Q000032:analysis / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains