Drugs that disrupt microtubuli do not inhibit lymphocyte activation

Abstract

LYMPHOCYTE activation by lectins is initiated by the binding of the lectin to a cell surface receptor. It is not known, however, how this event occurring on the cell membrane is converted into a signal that is transmitted to the cell interior. Edelman and coworkers^1–4 have advanced the hypothesis that lectin receptor sites may be attached to a submembranous microtubular system in a reversible way. This attachment could then determine the receptor mobility in the plane of the membrane and could also constitute a system for transmembrane signal transmission. The hypothesis is based, to a large extent, on the releasing effect that microtubule-disrupting drugs have on the inhibition of surface immunoglobulin cap formation in mouse B lymphocytes by concanavalin A (con A)^2,3. Furthermore, evidence has been presented that colchicine delayed and suppressed the appearance of con A-induced blast cells in human lymphocyte cultures, that there is a delay in the onset of DNA synthesis in cultures containing colchicine and that drug sensitivity decreases with increasing culture time in the presence of con A⁴. Cap formation of surface immunoglobulin (Ig) is a phenomenon restricted to Ig-bearing B lymphocytes and these cells are not activated by con A. It is felt therefore that observations on this population do not bear directly on the relationship between the con A receptors and microtubuli as a signal-transducing mechanism. The other observations are suggestive but not conclusive for such a role of the microtubular system.