Abnormal B lymphocyte function in thyroid glands from patients with Graves' disease.
Thyroid-infiltrating B lymphocytes from patients with Graves' disease were investigated in regard to their phenotypic profiles, cell size, cell cycle status, proliferative response to Staphylococcus aureus Cowan 1 (SAC), and spontaneous production of immunoglobulin G (IgG) and antithyroidal autoantibodies. Thyroid tissues and peripheral blood were obtained at the time of subtotal thyroidectomy of 27 Graves' patients who had been treated with thionamide drugs and iodide before operation. Two intrathyroidal mononuclear cell populations were obtained from these thyroid tissues. One cell population was isolated from the supernatants after mechanical disaggregation of the tissues and was defined as TG-1 cells. Another cell population, defined as TG-2 cells, was isolated from the supernatants of overnight cultures of the thyroid debris after enzymatic digestion. The percentages of B lymphocytes bearing activated markers and plasma cells (CD20+CD21-, IgM+IgD-, CD20+ transferrin receptor+, PCA-1+) were significantly higher in the TG-1 and TG-2 cell populations than in peripheral blood from Graves' disease patients and normal subjects. These phenotypic changes were accompanied by increased thyroid gland B lymphocyte cell size from patients with Graves' disease. The proliferative response of B lymphocytes to SAC was markedly lower in TG-1 and TG-2 cell populations than in peripheral blood cells from Graves' disease patients and normal subjects. B lymphocytes isolated from thyroid glands secreted significantly more IgG and antithyroidal autoantibodies than those from peripheral blood. Based on the findings of abnormalities in thyroid-infiltrating B lymphocytes, we suggest that activated B lymphocytes may induce the excessive production of antithyroidal autoantibodies in thyroid glands from patients with Graves' disease.
Ueki
Y
Y
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Otsubo
T
T
Kawabe
Y
Y
Shimomura
C
C
Tezuka
H
H
Nakao
H
H
Kawakami
A
A
Migita
K
K
Ishikawa
D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle; D002478:Cells, Cultured; D005260:Female; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013961:Thyroid Gland / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G