Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus arise from nonreactive and polyreactive precursors
| Autor: | Virginia Pascual, Klara Velinzon, Johannes F. Scheid, Klaus Abraham, Hedda Wardemann, Michel C. Nussenzweig, Brun Mietzner, Dorothee Stichweh, Thomas Tiller, Jose B. Gonzalez, Makoto Tsuiji |
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| Rok vydání: | 2008 |
| Předmět: |
Extractable nuclear antigens
medicine.drug_class Monoclonal antibody Autoantigens Immunoglobulin G Antigen Antibody Specificity medicine Humans Lupus Erythematosus Systemic Memory B cell skin and connective tissue diseases B cell Autoantibodies B-Lymphocytes Multidisciplinary Lupus erythematosus biology business.industry Autoantibody Antigens Nuclear Biological Sciences medicine.disease medicine.anatomical_structure Ribonucleoproteins Immunology biology.protein business Immunologic Memory |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 105(28) |
| ISSN: | 1091-6490 |
| Popis: | Persistent autoantibody production in patients with systemic lupus erythematosus (SLE) suggests the existence of autoreactive humoral memory, but the frequency of self-reactive memory B cells in SLE has not been determined. Here, we report on the reactivity of 200 monoclonal antibodies from single IgG+ memory B cells of four SLE patients. The overall frequency of polyreactive and HEp-2 self-reactive antibodies in this compartment was similar to controls. We found 15% of IgG memory B cell antibodies highly reactive and specific for SLE-associated extractable nuclear antigens (ENA) Ro52 and La in one patient with serum autoantibody titers of the same specificity but not in the other three patients or healthy individuals. The germ-line forms of the ENA antibodies were non-self-reactive or polyreactive with low binding to Ro52, supporting the idea that somatic mutations contributed to autoantibody specificity and reactivity. Heterogeneity in the frequency of memory B cells expressing SLE-associated autoantibodies suggests that this variable may be important in the outcome of therapies that ablate this compartment. |
| Databáze: | OpenAIRE |
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