Orderly pattern of development of the autoantibody response in (New Zealand White x BXSB)F1 lupus mice: characterization of target antigens and antigen spreading by two-dimensional gel electrophoresis and mass spectrometry
| Autor: | Nadine Machour, Roland Charlionet, Sandrine Thébault, Catherine Lange, Laurent Drouot, Marie Hubert, Danièle Gilbert, François Tron |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Heterogeneous nuclear ribonucleoprotein Immunogen Time Factors Immunology HL-60 Cells Biology Autoantigens Antigen-Antibody Reactions Mice Autoimmune Process Antigen Heat shock protein medicine Immunology and Allergy Animals Humans Lupus Erythematosus Systemic Electrophoresis Gel Two-Dimensional Crosses Genetic Autoantibodies Autoimmune disease Sex Characteristics Systemic lupus erythematosus Mice Inbred NZB Immune Sera Autoantibody medicine.disease Molecular biology Neoplasm Proteins Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Female Binding Sites Antibody |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 169(7) |
| ISSN: | 0022-1767 |
| Popis: | Immunoblots of a two-dimensional PAGE-separated HL-60 cell proteomic map and mass spectrometry were combined to characterize proteins targeted by autoantibodies produced by male (New Zealand White × BXSB)F1 (WB) mice that develop lupus and anti-phospholipid syndrome. Analysis of sera sequentially obtained from seven individual mice at different ages showed that six proteins, vimentin, heat shock protein 60, UV excision-repair protein RAD23, α-enolase, heterogeneous nuclear ribonucleoprotein L, and nucleophosmin, were the targets of the B cell autoimmune response, and that autoantibodies to them were synthesized sequentially in an orderly pattern that recurred in all the male WB mice analyzed: anti-vimentin first and anti-nucleophosmin last, with anti-RAD23 and anti-heat shock protein 60, then anti-α-enolase and anti-heterogeneous nuclear ribonucleoprotein L Abs occuring concomitantly. Anti-vimentin reactivity always appeared before anti-cardiolipin and anti-DNA Abs, suggesting that vimentin is the immunogen initiating the autoimmune process. The pattern of HL-60 proteins recognized by female WB sera differed from that of male sera, indicating that the Y chromosome-linked autoimmune acceleration gene is not an accelerator but a strong modifier of the autoimmune response. Thus, 1) combining two-dimensional PAGE and mass spectrometry constitutes a powerful tool to identify the set of Ags bound by autoantibodies present in a single serum and the whole autoantibody pattern of an autoimmune disease; 2) the diversification of the autoimmune response in male WB mice occurs in a predetermined pattern consistent with Ag spreading, and thus provides a useful model to further our understanding of the development of the autoantibody response in lupus. |
| Databáze: | OpenAIRE |
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