Frequent detection of thyroid peroxidase-specific IgG+ memory B cells in blood of patients with autoimmune thyroid disease.

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.

• 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)

Chemical References

• Antigens, CD19
• Autoantibodies
• Immunoglobulin G
• Iodide Peroxidase

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)