Interleukin-6 is a growth factor for nonmalignant human plasmablasts.
Interleukin-6 (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 preplasmablasts (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-2Ralpha) was increased 72 +/- 10-fold on activated B cells, but decreased and then disappeared on plasmablasts. Conversely, CD126 (IL-6Ralpha) 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.
Institut National de la Santé et de la Recherche Médicale U463 and Laboratoire d'Hématologie, Institut de Biologie, Nantes, France.
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D000328:Adult; D023201:CD40 Ligand / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002648:Child; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D015854:Up-Regulation
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D023201:CD40 Ligand