Selection of Immunoglobulin Variable Regions in Autoimmunity to DNA
| Autor: | Tony N. Marion, David M. Tillman, Nainn-Tsyr Jou, Robert J. Hill |
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| Rok vydání: | 1992 |
| Předmět: |
Models
Molecular Protein Conformation Molecular Sequence Data Immunology Population B-Lymphocyte Subsets Immunoglobulin Variable Region Autoimmunity medicine.disease_cause Autoimmune Diseases Mice chemistry.chemical_compound Immunoglobulin Idiotypes Antigen medicine Animals Lupus Erythematosus Systemic Immunology and Allergy Computer Simulation Amino Acid Sequence education Gene B cell education.field_of_study Hybridomas Genes Immunoglobulin Mice Inbred NZB biology Autoantibody DNA medicine.anatomical_structure Immunoglobulin M chemistry Antibodies Antinuclear Immunoglobulin G biology.protein Antibody Sequence Alignment Protein Binding |
| Zdroj: | Immunological Reviews. 128:123-149 |
| ISSN: | 1600-065X 0105-2896 |
| DOI: | 10.1111/j.1600-065x.1992.tb00835.x |
| Popis: | Results from our analyses of variable region gene usage among spontaneous anti-DNA antibodies in autoimmune mice have indicated that both the early IgM and later-appearing IgG autoantibodies to DNA are generated by clonally selected B cells. The recurrent usage of particular variable region genes among all the anti-DNA hybridomas analyzed and reported to date supports this hypothesis. The preferential expression of particular light and heavy chain variable region genes among selected populations of both IgM and IgG anti-DNA hybridomas likewise supports the hypothesis. Both IgM and IgG antibody-producing B cells are derived from the same clonal precursor population and may be derived from the same B cell clonal precursor within an individual mouse. The selective and recurrent expression of germline and somatically-derived structures that would be expected to promote protein binding to DNA within anti-DNA antibody variable regions, particularly arginines in both light and heavy chain complementarity-determining regions, indicates that DNA or DNA-containing complexes may be the antigen that stimulates anti-DNA antibody in autoimmune mice. The progressive increase in the specificity of spontaneous anti-DNA antibodies for native DNA as the autoimmune response matures from IgM to IgG likewise suggests that DNA may be the antigenic stimulus for spontaneous anti-DNA in autoimmune mice. A hypothetical, computer-generated model of anti-DNA antibody binding to DNA provides an interesting paradigm for the molecular basis of antibody specificity for DNA. |
| Databáze: | OpenAIRE |
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