VLA-4-dependent adhesion in follicular non-Hodgkin's lymphomas

The cellular contact between B cells and follicular dendritic cells (FDCs) in the germinal center is thought to play a key role in B-cell maturation and proliferation. The adhesion pathway through the very late antigen 4 (VLA-4) on the B cells and the vascular cell adhesion molecule 1 (VCAM-1) on the FDCs support this binding process. The neoplastic follicular centers in follicular non-Hodgkin's lymphomas (FNHLs) have similar structures and cellular components to those of normal germinal centers, but their interaction between B cells and FDCs may be functionally disturbed. In view of this we analyzed the interaction between VLA-4 and VCAM-1 molecules in the germinal center microenvironment, both in neoplastic and normal follicles. The structural characterization of FNHLs and reactive lymph nodes was studied with indirect immunohistochemical stainings using monoclonal antibodies against VLA-4, VCAM-1, and fibronectin, with special reference to the reaction pattern in the normal and neoplastic follicles. In the reactive follicular centers most B cells did not show a positive reaction for VLA-4, except for moderate reaction products in the B cells of the light zone. In FNHLs, on the other hand, most follicular center B cells were positive for VLA-4. The reaction patterns of VCAM-1 and fibronectin in both normal and neoplastic follicular centers were not basically different. To investigate the interaction of VLA-4 with VCAM-1 in both neoplastic and normal follicular centers, we performed a frozen-section binding assay, which found decreased binding between VLA-4 and VCAM-1 in FNHLs. The results of this study indicated that the microenvironment in neoplastic follicular centers is different from that in their normal counterparts, in terms of the characteristic distribution pattern of the VLA-4-positive B cells, and the functional deterioration of the VCAM-1 on FDCs.