Peripheral blood B-lymphocyte abnormalities associated with hyperthyroidism of Graves' disease

Abstract

Proportions of peripheral blood thymus-derived T lymphocytes (T cells) and bone-marrow-derived B-lymphocytes (B cells) were studied in twelve hyperthyroid patients and ninety-nine non-hyperthyroid control subjects including thirty-nine healthy individuals and sixty patients with various disorders. All hyperthyroid patients had Graves' disease and eight were untreated. The sheep erythrocyte (E)-rosetting technique was employed for enumeration of T cells and the immunofluorescent technique was used for identification of lymphocytes with surface immunoglobulins (SIg), a marker for B cells. The results showed that hyperthyroid patients had higher percentages of lymphocytes stainable for SIg, whereas their T-cell proportions were the same as our control values. In addition, approximately half or more of the fluorescein stainable lymphocytes reacted with each of the five antisera against individual heavy chain determinants, including the epsilon chain, indicating the presence of more than three Ig determinants on the same cell. The fluorescein-stainable cells did not form E rosettes. Blocking of the Fc receptor on lymphocytes by incubating the patients' cells with heat-aggregated human IgG or heated goat anti-bovine serum albumin (anti-BSA) failed to abolish the subsequent fluorescent staining of the cells. Incubation of patients' lymphocytes with non-fluorescent anti-epsilon inhibited the subsequent staining of cells with fluoresceinated anti-epsilon but not staining with fluoresceinated anti-mu or anti-gamma. Thus, the study revealed B-cell abnormalities associated with hyperthyroidism, manifested by the simultaneous presence of multiple Ig classes, including IgE, on a single B cell. Results of studies of incubation of the patients' plasmas with lymphocytes from health individuals and studies of SIg by overnight culture of the patients' lymphocytes with or without prior trypsinization suggested that the SIg was generated endogenously by the cell on which it resided.