Abstract |
Centrocytes in germinal centers on selection differentiate into plasma cells and/or memory B cells. Cells that have acquired autoreactivity by somatic mutation generally fail to undergo positive selection and die by apoptosis. Presence of isotype-switched high-affinity autoantibodies in serum of autoimmune patients suggests that autoreactive plasma cells eventually emerge from a germinal center reaction. Currently, it is still unclear to which extent the same is true for autoreactive memory B cells. To address this question, we have analyzed whether IgG-bearing memory B cells with specificity for thyroid peroxidase (TPO) can be found in blood of patients with autoimmune thyroid disease and in normal blood donors. Autoreactive TPO-specific IgG+ memory B cells were identified using a previously described assay combining two-step immunomagnetic enrichment with flow cytometric detection. Autoreactive IgG+ memory B cells were found in 65% of the patients with autoimmune thyroid disease and in 17% of normal blood donors; 40% of the latter had no detectable TPO-specific IgG in the serum. The specificity of enriched TPO-specific IgG+ memory B cells was confirmed by in vitro proliferation and differentiation into antibody-secreting cells at limiting dilution and analysis of the supernatants for the presence of TPO-specific IgG. Detection of TPO-specific IgG+ memory B cells in most patients with clinically manifested autoimmune thyroid disease and few normal blood donors may argue for a role of circulating memory B cells in onset of disease.
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Authors | Heike Leyendeckers, Eberhard Voth, Harald Schicha, Nicolas Hunzelmann, Paul Banga, Jürgen Schmitz |
Journal | European journal of immunology
(Eur J Immunol)
Vol. 32
Issue 11
Pg. 3126-32
(Nov 2002)
ISSN: 0014-2980 [Print] Germany |
PMID | 12385033
(Publication Type: Journal Article)
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Chemical References |
- Antigens, CD19
- Autoantibodies
- Immunoglobulin G
- Iodide Peroxidase
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Topics |
- Adolescent
- Adult
- Aged
- Antigens, CD19
(analysis)
- Autoantibodies
(blood)
- B-Lymphocytes
(immunology)
- Female
- Flow Cytometry
- Graves Disease
(immunology)
- Humans
- Immunoglobulin G
(blood)
- Immunologic Memory
- Immunomagnetic Separation
- Iodide Peroxidase
(immunology)
- Male
- Middle Aged
- Thyroiditis, Autoimmune
(immunology)
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