ACCESSORY CELLS MEDIATE HAIRY-CELL PROLIFERATION BY MECHANISM(S) INVOLVING BOTH ADHESION AND TNF-ALPHA SECRETION

The mechanisms responsible for hairy-cell (HC) growth both in vitro an d in vivo are still unclear. In a recent study we showed that monocyte s/macrophages induce HC proliferation in vitro. The purpose of the pre sent paper is to examine the specificity of this accessory cell effect and to establish the mechanism(s) involved. We demonstrate that the e ffect is not confined to monocytes/macrophages but is also potentially seen with a range of other cell types. However, at low accessory cell :HC ratios ( < 1:20) only human umbilical vein endothelial cells (HUVE C) and macrophages induce HC proliferation. We suggest that these obse rvations are of pathophysiological significance in relation to the clo se association frequently observed between HCs and endothelial cells/m acrophages in the liver and spleen of patients with hairy-cell leukaem ia (HCL) Regarding the mechanisms of the accessory cell effect, we sho w that both soluble factors and cell contact are important. A blocking anti-TNF alpha antibody abrogated the HC proliferation induced by HUV EC supernatant, indicating the involvement of this cytokine. Interacti on of HCs with HUVEC via CD11b and 11c leucocyte integrins was shown t o be important in the contact effect. Our demonstration of the involve ment of both cytokines and cell contact in HC proliferation is in acco rd with what is already known about the control of B-cell growth and d ifferentiation. More specifically, our results suggest that TNF alpha and interaction with endothelial cells/macrophages via leucocyte integ rins are involved in the proliferation of late B-cells of the maturati onal stage represented by HCs.