Mechanism of effector cell blockade: II. Colchicine fails to block effector cell blockade but enhances its reversal

Effector cell blockade, the suppression of antibody secretion by specific antigen, shares many features with the induction of B-cell unresponsiveness by either specific antigen (tolerance) or anti-immunoglobulin antibodies, and all three phenomena are likely to involve at least some mechanisms in common. Here we show that colchicine reverses a preexisting state of effector cell blockade induced in fluorescein-specific antibody-forming cells by preincubation with fluorescein-conjugated gelatin. Direct observation of fluoresceinated antigen on blockaded cells showed that in the presence of colchicine, but in general not in its absence, fluoresceinated antigen was capped. Similar results were obtained using a monoclonal hybridoma which secreted fluorescein-specific IgM antibody (FluIgM-1). Colchicine, however, had no influence on the degree of inhibition of antibody synthesis observed in FluIgM-1 cells during incubation in the continuous presence of soluble fluoresceinated gelatin. This finding suggested that colchicine-sensitive structures were not critical for the transmission of the negative signal involved in effector cell blockade, but did favour the persistence of the signal following the removal of excess antigen from the environment. These results and earlier studies provide evidence that the maintenance of the suppressive signal depends on the persistence of specific antigen on the cell surface and thus is likely to involve cell surface Ig. Colchicine-sensitive structures may not be an essential component in the Ig-mediated inactivation of the B cell.