IL-6, but not TPO, directly stimulates plasma cells. (A) Neither B cells nor plasma cells express the TPO receptor c-mpl. B220⁺/IgD⁺ B cells and CD138⁺⁺ plasma cells were isolated from bone marrow by FACS, and expression of the indicated genes was determined by reverse-transcribed PCR. In vitro–generated megakaryocytes were used as a high control for c-mpl expression. (B) Plasma cells do not respond to TPO. CD138⁺⁺ plasma cells were isolated from bone marrow and cultured as described earlier.¹¹  Total ASCs were quantified by ELISPOT. The percentage of plasma cells (ASCs) surviving for 3 days is shown when these cells were cultured: in the absence of specific stimulation, with either IL-6 or TPO alone, or with a combination of the 2 cytokines. Data are representative of 2 independent experiments. TPO was used in concentrations sufficient for the stimulation of megakaryopoiesis (supplemental Figure 8).