Differential effects of low and high concentrations of interleukin 6 on human B cells

In this report we have studied the functional effects of a wide range of interleukin 6 concentrations on human B cells. B cells purified from tonsils and from five of six spleens proliferated directly in a dose-dependent manner in the presence of low concentrations (1-100 pg/ml) of IL 6 whereas B cells from the sixth spleen proliferated only after in vitro anti-mu antibodies activation. Only large B cells (presumably in vivo activated B cells) were responsive to IL 6. High concentrations of IL 6 (1-10 ng/ml) did not trigger B cell proliferation but were able to up-regulate the expression of the B5 activation antigen on B cells, whereas the expression of two other B cell antigens (CD20 and CD23) was unchanged. At all concentrations of IL 6 tested (0.01-10 ng/ml) no B cell differentiation occurred after 7 days culture. Depletion before culture of B5+ cells from the B cell-enriched spleen cell preparation abolished both the proliferative effect and up-regulation of B5 antigen induced by IL 6, indicating that this lymphokine acted primarily on activated B cells. This differential effect of "low" and "high" concentrations of IL 6 on activated B cells may solve controversy on the role of IL 6 as an early or late agent in B cell maturation.