The genetic origin of murine lupus-associated autoantibodies

Details

Serval ID
serval:BIB_C86FA3F611A7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The genetic origin of murine lupus-associated autoantibodies
Journal
Immunology Letters
Author(s)
Kofler  R., Duchosal  M. A., Johnson  M. E., Aguado  M. T., Strohal  R., Kromer  G., Fassler  R.
ISSN
0165-2478 (Print)
Publication state
Published
Issued date
12/1987
Volume
16
Number
3-4
Pages
265-271
Language
english
Notes
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review --- Old month value: Dec
Abstract
Systemic lupus erythematosus and rheumatoid arthritis in human and murine systems are characterized by circulating autoantibodies and immune complex deposition in various organs causing tissue damage and disease. To define the molecular and clonotypic origin of these anti-self responses, and to determine whether abnormalities in Ig genes or somatic mechanisms generating autoantibody diversity may contribute to lupus etiology, we performed molecular analyses of the Ig germline gene organization and the Ig gene segments expressed in monoclonal autoantibodies from autoimmune mice. Comparative restriction fragment length polymorphism analysis of a large number of Ig gene loci from autoimmune and normal mice indicated that (a) lupus can develop in different Ig heavy and kappa light chain variable region gene haplotypes, and (b) the Ig germline genes in lupus mice might be normal. To determine whether autoantibodies are encoded by unique Ig gene segments present in the normal germline repertoire, but not expressed in exogenous responses, we compared nucleic acid sequences encoding lupus autoantibodies and antibodies against foreign antigens. Similar, and in some instances even identical, gene segments were expressed in both types of antibodies, indicating that anti-self and anti-foreign responses use the same, or at least an overlapping, germline gene repertoire. A large variety of Ig variable, diversity, and joining gene segments encoded these autoantibodies with different specificities. Hence, the overall murine lupus-associated anti-self response may be essentially unrestricted. Furthermore, limited evidence has been obtained that both germline genes and somatically mutated genes encode autospecificity, making gross abnormalities in mechanisms for somatic mutation of Ig variable genes unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)
Keywords
Animals Antibody Diversity Autoantibodies/*genetics Humans Immunoglobulins/genetics Lupus Erythematosus, Systemic/genetics/*immunology Mice Mutation
Pubmed
Web of science
Create date
25/01/2008 16:24
Last modification date
20/08/2019 16:43
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