Interleukin-1 stimulation of human B-lymphoblast differentiation

Abstract

Transformed B-cell lines have provided useful tools for analyzing B-cell responses to growth and differentiation factors. SKW 6.4 is a human B-lymphoblastoid line that differentiates in response to B-cell differentiation factor (BCDF) but not to other T-cell-derived lymphokines. The present studies were undertaken to determine whether monocyte-derived factors such as interleukin-1 (IL-1) could also promote the maturation of SKW 6.4 cells. Cells were cultured with and without supernatants derived from adherent monocytes of normal individuals. The number of Ig-producing plaque-forming cells in control media cultures gradually increased over a period of 4 days. Monocyte supernatants caused a 3- to 10-fold further increase in the number of IgM-secreting cells over that found in control media cultures. this stimulation by monocyte supernatants was maximal on the third or fourth day of culture and was not accompanied by an increase in proliferation. Recombinant IL-1 added to cultures of SKW 6.4 also produced a dose-related increase in the number of IgM-secreting cells without stimulating proliferation. A polyclonal antiserum against IL-1 prevented the increase in IgM-secreting cells which occurred with the addition of monocyte supernatants. Finally, IL-1 activity was detected in unstimulated SKW 6.4 supernatants. We conclude from these studies that SKW 6.4 cells both secrete IL-1 and differentiate in response to exogenous IL-1. SKW 6.4 may therefore provide a useful tool for future studies on mechanisms of IL-1-induced B cell maturation. It is possible that the basal numbers of IgM-secreting cells seen in unstimulated cultures results from an autocrine mechanism of IL-1-induced differentiation. Finally, care should be taken to exclude IL-1 from supernatants that are being tested for BCDF activity using SKW 6.4 cells.