Reactive plasmacytoses are expansions of plasmablasts retaining the capacity to differentiate into plasma cells

Circulating plasma cells in 10 cases of reactive plasmacytosis had a shared phenotype with early plasma cell (CD19(+) CD38(+) CD138(+) CD40(+) CD45(+) CD11a(+) CD49e(-) CD56(-)). In most cases, a minor subpopulation of CD28() plasma cells was also detected. Reactive plasma cells were highly prolife rative, suggesting the presence of circulating progenitors (plasma-blasts). After CD138(+) plasma cell removal, highly proliferative CD138(-) plasmabl asts differentiated into CD138(+) plasma cells within a few days. This diff erentiation, which was associated with increased CD38 and decreased HLA-DR expression, was further confirmed by a large increase in intracellular Ig c ontent (associated with Ig secretion) and was concomitant with extensive se cretion of interleukin-6 (IL-6). The addition of neutralizing anti-IL-6 and anti-CD126 (IL-6 receptor) monoclonal antibodies totally prevented Ig secr etion and cell differentiation by inducing apoptosis of plasmablasts, which indicates that IL-6 is an essential survival factor for plasmablasts. This report provides the first characterization of normal plasmablasts and show s that their phenotype is not exactly that of multiple myeloma cells, (C) 1 999 by The American Society of Hematology.