Follicular non-Hodgkin's lymphoma cell adhesion to normal germinal centers and neoplastic follicles involves very late antigen-4 and vascular cell adhesion molecule-1

Abstract

Follicular lymphomas recapitulate the architecture of germinal centers (GCs) of normal secondary lymphoid follicles. Using an in vitro binding assay, it has recently been demonstrated that the normal B lymphocytes bind to GCs. This interaction is mediated by a receptor-ligand pair consisting of the beta 1 integrin very late antigen 4 (VLA-4) on the B cell, and the vascular cell adhesion molecule-1 (VCAM-1) expressed on follicular dendritic cells (FDC). Considering the similarities between follicular lymphomas and normal GCs, the adhesive interaction of follicular non-Hodgkin's lymphoma (NHL) cells and GCs was examined. Cells isolated from 16 of 24 cases of follicular NHL bound to normal GCs. Neoplastic follicles could similarly support the binding of follicular NHL cells. This adhesion was inhibited by monoclonal antibodies (MoAbs) directed against VLA-4 and VCAM-1. This supports the hypothesis that the neoplastic follicles used the identical adhesive interactions responsible, at least in part, for the localization of normal B cells to GCs. Adhesion receptors have an important role in the regulation of normal lymphoid cell proliferation, differentiation, and localization. Therefore, an understanding of the adhesive interaction of follicular NHL cells with GCs may provide insight into the clinical and biologic behavior of these diseases.

The stromal composition of malignant lymphoid aggregates in bone marrow: variations in architecture and phenotype in different B‐cell tumours

“…These interactions may be mediated, in part, through CD40-ligand expressed on T-cells and CD40 present on both lymphoma cells and marrow stroma (Tsubata et al, 1993;Kim et al, 1994;Merville et al, 1995). The upregulation of CD40 we observed on bone marrow stroma in these areas would support a role for this pathway (Koopman et al, 1991;Freedman et al, 1992;Ghia et al, 1998;Voorzanger-Rousselot et al, 1998).…”

Mantle cell lymphomas acquire increased expression of CCL4, CCL5 and 4‐1BB‐L implicated in cell survival

“…4‐1BB, which is a member of the TNF‐receptor superfamily, was recently shown to be expressed on FDCs, by us41 and others 23. Interestingly, the follicles in nodular MCLs are normally defined by a prominent FDC mesh‐work,2 and FDCs have also been shown to be involved in the survival of NHLs, although the specific interactions were then not elucidated 42, 43. Thus, an interaction between 4‐1BB on FDC and 4‐1BB‐L on MCL may infer a growth advantage and increased survival of the tumor cells, although this hypothesis needs to be confirmed.…”

MCP‐1 modulates chemotaxis by follicular lymphoma cells

“…Results are expressed as the absolute number of cells that migrated and are representative of three independent determinations. (Freedman et al, 1992). It is not known whether FL cells migrate toward FDCs, but production of SDF-1 and IL-8 by FDCs suggests that they might induce FL cell migration.…”