Granuloctye-macrophage colony-stimulating factor as an autocrine survival factor for mature normal and malignant B lymphocytes

The role of GM-CSF in B cell (patho)physiology is unclear. Although B cells can respond to GM-CSF, there is controversy concerning the extent to which various resting and activated B cell types can themselves produce this cyt okine, and the possibility that it can function in an autocrine fashion has not previously been considered. The aim of the present study was to addres s these issues using hairy cells (HCs) and chronic lymphocytic leukemia cel ls, two intrinsically activated mature malignant B cell types (with activat ion being more uniform and more pronounced in HCs), Normal B cells were use d for comparison. Using a number of techniques, we demonstrated the constit utive production of GM-CSF by all three cell types and showed that the cyto kine was biologically active, GM-CSF mRNA and protein were increased after cell activation by PMA, and constitutive production of the cytokine was hig hest in HCs, suggesting that the level of GM-CSF production is influenced b y cell activation. Because GM-CSF is known to be antiapoptotic for myeloid cells, we used blocking anti-GM-CSF Abs to examine the contribution of auto crinely produced cytokine to cell survival. The Abs produced marked reducti on in the in vitro survival of HCs, chronic lymphocytic leukemia cells, and normal B cells by promoting apoptosis, Taken together, these findings sugg est that, in combination with other known rescue factors, autocrinely produ ced GM-CSF may contribute to normal and malignant B cell survival in vivo.