T-cell derived cytokines co-stimulate proliferation of CD40-activated germinal centre as well as follicular lymphoma cells.

Follicular lymphomas, the malignant counterparts of normal germinal centre (GC) B-cells, grow in vivo in close association with polyclonal T-cells, predominantly from the T-helper cell type. T-cell-derived growth factors are involved in the development of GC B-cells. However, their role in the pathogenesis of follicular lymphomas has not been clearly defined. We investigated the co-stimulatory activity of 14 cytokines (interleukin-1 to -8, IL-10, IL-13, INF-alpha, TNF-alpha, GM-CSF and SCF) on the proliferation of CD40-activated follicular lymphoma cells in comparison to tonsillar GC B-cells. Tonsillar GC B-cells (n = 4), malignant cells from diagnostic lymph node biopsies of patients with follicular (n = 4) or transformed (n = 4) lymphomas were grown on irradiated CD40-ligand transfectants, with and without cytokines. [3H]-thymidine uptake was measured at day 7. IL-10 and IL-4 proved to be the most potent co-stimulators of proliferation of tonsillar GC B-cells, whereas proliferation of follicular lymphoma cells was co-stimulated by IL-4. The fact that IL-4 is a T-cell derived cytokine, suggests that lymphoma infiltrating T-cells play a role in the growth of these malignancies. Moreover, proliferation of both non-neoplastic tonsillar GC B-cells and follicular lymphomas is co-stimulated by T-cell derived cytokines, indicating that responsiveness to paracrine factors may not be a characteristic of the malignant phenotype.