Autoimmune syndrome after neonatal induction of tolerance to alloantigens: analysis of the specificity and of the cellular and genetic origin of autoantibodies

Details

Serval ID
serval:BIB_6CDE59DCEFF8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Autoimmune syndrome after neonatal induction of tolerance to alloantigens: analysis of the specificity and of the cellular and genetic origin of autoantibodies
Journal
Autoimmunity
Author(s)
Schurmans  S., Merino  J., Qin  H. Y., Kramar  G., Duchosal  M., Skalli  O., Benzonana  G., Gabbiani  G., Lambert  P. H.
ISSN
0891-6934 (Print)
Publication state
Published
Issued date
1991
Volume
9
Number
4
Pages
283-291
Language
english
Notes
Journal Article Research Support, Non-U.S. Gov't
Abstract
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.
Keywords
Animals Animals, Newborn Antibody Specificity Antigens, CD Antigens, CD5 Autoantibodies/*biosynthesis/genetics Autoimmune Diseases/*etiology/genetics/immunology B-Lymphocyte Subsets/immunology Genes, Immunoglobulin H-2 Antigens Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred CBA Syndrome
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Web of science
Create date
25/01/2008 16:24
Last modification date
20/08/2019 15:26
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