Interleukin-6 is a growth factor for nonmalignant human plasmablasts

Interleukin-g (IL-6), although often regarded as a B-cell differentiation factor, was recently described as the essential survival factor for human plasmablasts in vivo in reactive plasmacytosis, The present study reinvestigated the roles of IL-6 and IL-2 in the generation of plasma cells from human memory B cells in vitro. The cells involved in this differentiation process were identified as preplasma-blasts (CD20(+/-)CD38(+/-)CD138(-)), plasmablasts (CD20(-)CD38(++)CD138(-)), and early plasma cells (CD20(-)CD38(+++)CD138(+++)). IL-2 or IL-10 induced a strong generation of plasmablasts and early plasma cells (PCs), Compared to IL-2 or IL-10, IL-6 alone was inefficient at PC generation, However, when combined with IL-2 or IL-10, IL-6 enhanced generation of early PCs. Moreover, anti-IL-6 monoclonal antibody markedly reduced IL-2-induced generation of early plasma cells, but not of plasmablasts. These roles of IL-2 and IL-6 were consistent with the difference in the expression of their respective receptors (R), CD25 (IL-2R alpha) was increased 72 +/- 10-fold on activated B cells, but decreased and then disappeared on plasmablasts, Conversely, CD126 (IL-6R alpha) was barely expressed on activated B cells, but increased 18 +/- 2-fold on preplasmablasts, Finally, IL-6 enhanced the proliferation (2-fold increase) of IL-2-generated plasmablasts, In conclusion, the data indicate that IL-6 is a growth factor for nonmalignant human plasmablasts, (Blood, 2001; 97:1817-1822) (C) 2001 by The American Society of Hematology.