Differential Expression of Ca(2+)-binding Proteins on Follicular Dendritic Cells in Non-neoplastic and Neoplastic Lymphoid Follicles

We studied the Ca(2+)-capture ability of follicular dendritic cells (FDCs) in tonsillar secondary lymphoid follicles (LFs) and the expression of six Ca(2+)-binding proteins (CBPs), caldesmon, S-100 protein, calcineurin, calbindin-D, calmodulin, and annexin VI in LFs of various lymphoid tissues and caldesmon and S-100 protein in neoplastic follicles of follicular lymphomas. First, Ca(2+)-capture cytochemistry revealed extensive Ca(2+) capture in the nuclei and cytoplasm of FDCs, but little or none in follicular lymphocytes. All six CBPs were localized immunohistochemically in the LFs and were always present in the basal light zone. Immunoelectron microscopic staining of FDCs was classified into two patterns: caldesmon was distributed in the peripheral cytoplasm like a belt; S-100 protein, calcineurin, calbindin-D, and calmodulin were distributed diffusely in the cytosol. Annexin VI was, however, negative on FDCs. Immunocytochemistry also demonstrated CBP-positive FDCs within FDC-associated clusters isolated from germinal centers. In situ hybridization revealed diffuse calmodulin mRNA expression throughout the secondary LFs. These data indicate that the CBPs examined may regulate Ca(2+) in the different subcellular sites of FDCs, and the roles of CBPs may be heterogeneous. We also investigated the distribution of caldesmon and S-100 protein in follicular lymphomas on paraffin-embedded tissue sections. FDCs within grades I and II neoplastic follicles clearly expressed caldesmon, but not S-100 protein, except a part of grade II neoplastic follicles. FDCs within grade III follicles showed no caldesmon, but frequently expressed S-100 protein. These results demonstrate that the caldesmon and S-100 protein staining patterns of grade I follicular lymphomas are different from those of grade III follicular lymphomas and suggest that FDC networks in grade I neoplastic follicles may be similar to those in the light zone within non-neoplastic follicles, FDC networks in grade III neoplastic follicles may be similar to those in dark and basal light zones within non-neoplastic follicles, and grade II follicles may be intermediate between grade I and grade III follicles.