Autoimmune syndrome after neonatal induction of tolerance to alloantigens: analysis of the specificity and of the cellular and genetic origin of autoantibodies.
BALB/c mice neonatally injected with 10(8) semiallogeneic (C57BL/6 x BALB/c)F1 spleen cells become tolerant to the H-2b alloantigens, but also develop a wide range of autoimmune manifestations characteristic of systemic lupus erythematosus (SLE). Indeed, in these mice, the presence of a hypergammaglobulinaemia, autoantibodies--including anti-ssDNA, anti-platelet, thymocytotoxic and rheumatoid factor antibodies--circulating immune complexes, cryoglobulins as well as renal glomerular deposition of immunoglobulins have been observed. In this study, we have shown that the allogenic effect and B cell chimaerism which characterize these F1 cell-injected mice is associated with the expression of a large spectrum of autoantibodies, including anti-ssDNA and anti-cytoskeleton antibodies, and that these autoantibodies are not multispecific. We took advantage of the fact that, in this model, autoantibodies are exclusively produced by F1 donor B cells to inject newborn BALB/c mice with F1 Xid spleen cells lacking the CD5+ B cell subset. Injection of 2 x 10(8) F1 Xid spleen cells triggers the production of anti-ssDNA as well as anti-BrMRBC antibodies, and these mice developed tissue lesions. Finally, analysis of the VH gene family expressed by monoclonal autoantibodies derived from F1 cell-injected mice showed that they used the 2 largest families J558 and 7183. These results suggest that the allogenic effect and B cell chimerism which characterize the neonatal induction of tolerance to MHC alloantigens is associated with the selective triggering of autoreactive B cells producing monospecific IgG autoantibodies. They also imply that upon stimulation by persisting alloreactive CD4+ T cells, either CD5- B cells are able to produce autoantibodies or autoantibody-producing CD5+ B cells can differentiate from Xid spleen cells.
Schurmans
S
S
WHO Immunology Research and Training Center, Geneva, Switzerland.
Merino
J
J
Qin
H Y
HY
Kramar
G
G
Duchosal
M
M
Skalli
O
O
Benzonana
G
G
Gabbiani
G
G
Lambert
P H
PH
D000818:Animals; D000831:Animals, Newborn; D000918:Antibody Specificity; D015703:Antigens, CD; D001323:Autoantibodies / Q000096:biosynthesis* / Q000235:genetics; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology; D018956:CD5 Antigens; D005803:Genes, Immunoglobulin; D006183:H-2 Antigens; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013577:Syndrome
D015703:Antigens, CD; D001323:Autoantibodies; D018956:CD5 Antigens; D006183:H-2 Antigens