Synthesis and release of B-lymphocyte stimulator from myeloid cells

B-lymphocyte stimulator (BLyS) is a recently identified novel member of the tumor necrosis factor ligand superfamily shown to exist in a membrane-boun d and soluble form, BLyS was found to be specifically expressed on cells of myeloid lineage and to selectively stimulate B-lymphocyte proliferation an d immunoglobulin production. The expression of a cytokine involved in poten tiation of humoral immune responses, such as BLyS, is expected to be strict ly controlled. The goal of the present study was to examine regulation of B LyS levels in monocytic cells in response to cytokines and during their dif ferentiation to macrophages and dendritic cells. The presence of BLyS on th e cell surface and in the culture medium of both normal blood monocytes and on tumor cells of myelomonocytic origin was demonstrated, BLySgene express ion and levels of membrane-associated and soluble BLyS were found to be reg ulated by cytokines, in particular interferon (IFN)-gamma and to a lesser e xtent interleukin-10 (IL-10), The expression of BLyS on monocyte membranes was retained following differentiation into macrophages, but detection on t he surface of monocyte-derived dendritic cells required stimulation with IF N gamma. Both IFN-gamma and IL-10 enhanced the release of soluble BLyS that was active in B-cell proliferation assays. Cells transfected with BLyS com plementary DNA mutated in a predicted cleavage site failed to release BLyS into the culture medium, thereby suggesting that soluble BLyS was derived f rom the membrane form. These results provide further support for an importa nt role for BLyS expressed in myeloid cells in B-cell expansion and antibod y responses, (C) 2001 by The American Society of Hematology.