B-cell compartment in the thymus of patients with myasthenia gravis and control subjects.

Abstract

An increased number of CD19, 20, and 22 positive B cells, compared to the number of Ig-positive cells, is regularly found in the thymic medulla of normal thymus, suggesting that a B-cell population normally resides in thymic medulla that lacks Ig expression. However, some of the CD20-positive cells seem to co-express keratin and MR19, suggesting an epithelial origin. The medullary B cells found in normal thymus could be precursors of the tumor cells in "mediastinal clear cell lymphomas of B-cell type." In follicular hyperplasia in MG, the medullary epithelial network is deformed and partly destroyed, and the interlobular/perivascular spaces are expanded. Follicles with follicular dendritic cells are found in both interlobular/perivascular spaces and "punched out" lesions in the medullary epithelium. The B cells are greatly increased in MG thymuses compared with control thymuses. These cells are found mainly in the follicles, but they are also dispersed in the medulla and the interlobular/perivascular spaces. The immunophenotype and distribution of B and T cells as well as the follicular dendritic cells in the hyperplastic follicles are similar to those of reactive follicles in lymph nodes. Our findings are consistent with the contention that in MG there is an autoimmune activation of B cells that normally reside in the thymic medulla. This activation leads initially to follicular hyperplasia in the medullary epithelium with destruction of medullary epithelial cells. The prolonged immune reaction in the autoimmune process induces a fibronectin-rich stroma formation and increased vascularization. The result is a remodeling of the thymic architecture with expansion of the perivascular/interlobular spaces replacing the destroyed medulla.