¹Institute of Cell Signalling and School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK

²MRC Centre for Immune Regulation, University of Birmingham Medical School, Birmingham B15 2TT, UK

Correspondence to: C D Gregory, Institute of Cell Signalling and School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK, Tel: +44 115 970 9370; Fax: +44 115 970 9926; E-mail: Chris.Gregory@nottingham.ac.uk

Edited by M Piacentini

Burkitt lymphoma (BL) cells retain a high inherent propensity to undergo apoptosis indicating that net growth of the tumour population in vivo is likely to be influenced profoundly by its micro-environment. Here we investigate micro-environmental factors that affect BL-cell survival in vitro. We show that survival, and consequently net production, of tumour cells is enhanced by autocrine factors and, to a greater extent, by paracrine factors provided by relevant stromal elements of the tumour (fibroblasts and follicular dendritic cells) and by macrophages. Promotion of BL-cell survival by paracrine elements was mediated by cell/cell contact and by short-range soluble factor(s). IL-4, IL-10 and TNF- promoted, whereas TGF-1 inhibited, tumour-cell production. Macrophages engaged in phagocytosis of apoptotic BL cells were less effective than untreated macrophages in supporting net expansion of BL populations. These results suggest that the net production of tumour cells in BL is supported by multiple micro-environmental factors that modulate apoptosis. Cell Death and Differentiation (2000) 7, 59-69.

apoptosis; B-cell; Burkitt; lymphoma; micro-environment; macrophage

bFGF, basic fibroblast growth factor; BL, Burkitt lymphoma; CD40L, CD40 ligand; EGF, epidermal growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; HFF, human foetal fibroblast; IGF, insulin-like growth factor; IL, interleukin; LPS, lipopolysaccharide; PDGF, platelet-derived growth factor; TGF, transforming growth factor; TNF, tumour necrosis factor