Frequent detection of thyroid peroxidase-specific IgG+ memory B cells in blood of patients with autoimmune thyroid disease.
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.
Leyendeckers
Heike
H
Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
Voth
Eberhard
E
Schicha
Harald
H
Hunzelmann
Nicolas
N
Banga
Paul
P
Schmitz
Jürgen
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000032:analysis; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007156:Immunologic Memory; D018189:Immunomagnetic Separation; D007453:Iodide Peroxidase / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D018941:Antigens, CD19; D001323:Autoantibodies; D007074:Immunoglobulin G; D007453:Iodide Peroxidase