Thyroid-Infiltrating B Lymphocytes in Graves' Disease are Related to Marginal Zone and Memory B Cell Compartments

Abstract

B lymphocytes that infiltrate the thyroid (Thy-B cells) in Graves' patients appear to be implicated in the pathophysiology of this disorder. The goal of the present study was to examine the nature of these Thy-B cells. To this end, Thy-B lymphocytes were isolated from surgical thyroidal samples, and their phenotype was determined by using mouse monoclonal antibodies (mAb) directed against a wide variety of surface markers, followed by flow cytometry multicolor analysis. The results show that most Thy-B cells (≅60%) exhibited IgM⁺ IgD^{low to-} surface immunoglobulin (Ig) profile, whereas the minor cell fraction (≅30%) consisted of switched IgG⁺ memory B lymphocytes. Thy-B cells expressed low levels of CD5, CD23, and CD62L, which distinguished them from the resting B-cell pool, the major B-cell subset in the blood. In addition, they lacked CD38, CD10, and CD71, characteristic molecules for the germinal center B lymphocytes. In addition, Thy-B lymphocytes showed peculiar patterns both of adhesion molecules (CD62L^-, CD44^intermediate), and of activation molecules (CD69⁺, CD80⁺, and, in part, CD95⁺). Taken together, these results suggest that the Thy-B lymphocyte subset consists of a combination of IgM⁺ B cells resembling marginal zone B lymphocytes, and isotype-switched memory B cells.