Plasma cell generation from B-lymphocytes via CD27/CD70 interaction.

To produce antibodies, the differentiation of B cells into antibody-secreting cells, plasma cells, is required. We describe that ligation of CD27, which belongs to the tumor necrosis factor receptor (TNFR) family and is a memory marker of B cells, yields crucial signals that positively control the entry of B cells into the pathway to plasma cells. The triggering via CD27 by CD27 ligand (CD70) on purified peripheral blood B cells yielded an increase in the number of plasma cells in the presence of interleukin-10 (IL-10). The differentiation into plasma cells by a combination of IL-10 and CD70-transfectants occurred in CD27+ B cells, but not in CD27- B cells. Moreover, the addition of IL-2 to the IL-10 and CD70-transfectants greatly induced the differentiation into plasma cells. In the presence of only IL-2, IL-4 or IL-6, CD70-transfectants did not promote the differentiation into plasma cells. On the other hand, CD40 signaling increased the expansion of a B cell pool from peripheral blood B cells primarily activated by IL-2, IL-10 and anti-CD40 mAb. These data demonstrate that CD27 ligand (CD70) is a key molecule to direct the differentiation of CD27+ memory B cells toward plasma cells in cooperation with IL-10.