Differences in Thyroid-Infiltrating B Lymphocytes in Patients with Graves' Disease: Relationship to Autoantibody Detection

Abstract

Objective: Thyroid-infiltrating B (Thyr-B) lymphocytes are thought to play an important role in the pathogenic mechanisms underlying Graves' disease. Design and methods: In this study, a broad phenotypic analysis of these cells has been performed in 15 consecutive patients who underwent thyroidectomy. Results: Data reveal the occurrence of two distinct types of Thyr-B cell infiltrates. Type 1 was present in most of the cases (10/15) and consisted of a combination of IgM⁺ IgD^{low to-} B lymphocytes showing features of marginal zone B cells, and IgG⁺ classic memory B cells. In contrast, in 5 of the 15 cases, a second type of Thyr-B cell infiltrate occurred, exhibiting the profile IgM^- IgD^- CD44^{low to-} CD38⁺⁺ CD71⁺ CD95⁺. This phenotype is highly suggestive of germinal center (GC) B cells, a finding not always anticipated from routine histologic examination. The presence of these ectopic GC was closely associated with the elevated serum level of anti-thyroid peroxidase (TPO), but not with anti-thyrotropin receptor (TSHR), autoantibodies. Moreover, local active anti-thyroglobulin (Tg) antibody secretion was only detected in cultures of type 2 Thyr-B cells. Conclusion: These findings indicate that high titers of anti-TPO, but not anti-TSHR antibody, might be associated with intrathyroidal GC development.