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
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
Pubmed
Web of science
Create date
25/01/2008 16:24
Last modification date
20/08/2019 15:26