Studies on leukocyte migration inhibitory factor (LIF) produced by activated T and B cells

Human T and B cells produce leukocyte migration inhibitory factor (T-LIF and B-LIF, resp.). Some properties of T-LIF and B-LIF were compared in this study. T cells were activated by PHA or by a synthetic peptide, representing the Epstein-Barr virus (EBV) nuclear antigen, EBNA1, B cells were exposed to polyclonal activators, anti-IgM or EBV. The kinetic profile of T-LIF and B-LIF released into the culture supernatants from 6 hrs until 24 hrs after activation was identical and termed "peak 2". B cells, in addition, released LIF activity after 30-60 min ("peak 1"). Molecular weight determinations by HPLC gel filtration showed that both peaks contained activity in fractions around 70 Kd. B-LIF also showed a lower molecular weight activity peak. T-LIF and B-LIF activity was equally abrogated with a rabbit anti- human LIF serum. Polymixin-B, a protein kinase C inhibitor and verapamil, a calcium channel-blocking drug, inhibited antigen-induced T-LIF and B-LIF present in "peak 2", whereas the lysosomotropic chloroquine abrogated "peak 1" early activity. We conclude that T-LIF and B-LIF are identical or very similar molecules. B cells might store presynthetized LIF in lysosomic granulae which will be degranulated very early after activation. The second peak represents de novo LIF synthesis, that requires external calcium and intact protein kinase C activity.