VLA-4-DEPENDENT ADHESION IN FOLLICULAR NON-HODGKINS-LYMPHOMAS

The cellular contact between B cells and follicular dendritic cells (F DCs) in the germinal center is thought to play a key role in B-cell ma turation and proliferation. The adhesion pathway through the very late antigen 4 (VLA-4) on the B cells and the vascular cell adhesion molec ule 1 (VCAM-1) on the FDCs support this binding process. The neoplasti c follicular centers in follicular non-Hodgkin's lymphomas (FNHLs) hav e similar strictures and cellular components to those of normal germin al centers, but their inter-action between B cells and FDCs may be fun ctionally disturbed. In view of this we analyzed the interaction betwe en VLA-4 and VCAM-1 molecules in the germinal center microenvironment, both in neoplastic and normal follicles. The structural characterizat ion of FNHLs and reactive lymph nodes was studied with indirect immuno histochemical stainings using monoclonal antibodies against VLA-4, VCA M-1, and fibronectin, with special reference to the reaction pattern i n the normal and neoplastic follicles. In the reactive follicular cent ers most B cells did not show a positive reaction for VLA-4, except fo r moderate, reaction products in the B cells of the light zone. In FNH Ls, on the other hand, most follicular center B cells were positive fo r VLA-4. The reaction patterns of VCAM-1 and fibronectin in both norma l and neoplastic follicular centers were not basically different. To i nvestigate the interaction of VLA-4 with VCAM-1 in both neoplastic and normal follicular centers, we performed a frozen-section binding assa y which found decreased binding between VLA-4 and VCAM-1 in FNHLs. The results of this study indicated that the microenvironment in neoplast ic follicular centers is different from that in their normal counterpa rts, in terms of the characteristic distribution pattern of the VLA-4- positive B cells, and the functional deterioration of the VCAM-1 on FD Cs.