Follicular Dendritic Cell Meshwork in Angioimmunoblastic T-Cell Lymphoma Is Characterized by Accumulation of CXCL13<sup>+</sup> Cells

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is considered to originate from follicular helper T (TFH) cells. Currently, neoplastic cells in AITL are considered to express CXCL13 as a tumor marker. However, the identification of CXCL13(+) cells remains unclear in terms of whether they are neoplastic cells (or TFH cells) or follicular dendritic cells (FDCs) in both AITL and normal germinal centers. Therefore, the exact identification of CXCL13(+) cells was performed using 33 cases of AITL and normal germinal centers. Single-labeling immunohistochemistry and double-labeling immunofluorescent microscopy first confirmed that CXCL13 was expressed mainly in FDCs in the normal germinal centers. In 28 of 33 AITL cases, CXCL13 was expressed mainly in FDCs as a meshwork pattern, which was associated with CXCL13(+) neoplastic cells. In the other five cases, CXCL13 was expressed mainly in neoplastic cells, which were densely distributed in and around the FDC meshwork. These findings indicate the abundance of CXCL13(+) cells in the FDC meshwork irrespective of the cell type. Triple-labeling immunofluorescent microscopy showed that the CXCL13(+) FDC meshwork in AITL harbored both neoplastic cells and B cells. CXCR5, the cognate receptor of CXCL13, was expressed in neoplastic cells in AITL. The present study suggests that neoplastic cells in AITL preserve a certain level of TFH-cell function since neoplastic cells and B cells are closely enmeshed in the CXCL13(+) cell-rich FDC meshwork in a similar way as in normal germinal centers.