HIV-1 INDUCTION OF CD40 ON ENDOTHELIAL-CELLS PROMOTES THE OUTGROWTH OF AIDS-ASSOCIATED B-CELL LYMPHOMAS

Human immunodeficiency virus (HIV)-1 infection is associated with the development of aggressive extranodal B-cell non-Hodgkin's lymphomas. U sing microvascular endothelial cell (MVEC)enriched bone marrow stromal cultures, HIV infection of stromal MVECs from lymphoma patients induc ed the outgrowth of malignant B cells. MVECs were the only HIV-infecte d cells in the stroma, and purified brain MVECs also induced a phenoty pe supportive of neoplastic B-cell attachment and proliferation. HIV i nfection of MVECs stimulated surface expression of CD40 and allowed pr eferential induction of the vascular cell adhesion molecule VCAM-1 aft er CD40 triggering. B-lymphoma cells expressed the CD40 ligand (CD40L) , and blocking of CD40-CD40L interactions between HIV-infected MVECs a nd B-lymphoma cells inhibited B-cell attachment and proliferation. The se observations suggest that HIV promotes B-lymphoma cell growth throu gh facilitating attachment of lymphoma cells to HIV-infected MVECs and represent a novel mechanism through which viruses may induce malignan cies.