Effect of vinblastine on the early events in the humoral immune response of mice to SRBC.

The effect of vinblastine (VLB), a mitotic blocking agent, on the number of plaque-forming cells (PFC) and on the metabolic activities of spleen cells of mice reimmunized with SRBC was studied. When VLB (75 mug/mouse) and antigen were administered simultaneously, the number of pfc, on the 4th day after immunization, was reduced to 40% of control levels. However, when the same amount of VLB was administered to mice 24 h after immunization, it reduced the number of PFC to 10% of control levels. The possibility that VLB exerts a specific cytotoxic effect on preformed PFC either in vivo or in vitro was ruled out. A direct profound effect of VLB on antigen-stimulated cells was observed when VLB was injected 24 h after reimmunization, and the incorporation rates of radioactive precursors into macromolecules by spleen cells were measured at 4-hour intervals. VLB suppressed completely the antigen-induced peak of 3H-thymiding incorporation, while it had no effect on the incorporation rate of 3H-uridine and only a slight effect on the incorporation rate of 3H-amino-acids by the same cells. The results suggest that the decrease in number of PFC caused by injection of VLB 24 h after immunization is due to prevention by VLB, of precursor cells from going through a critical cell division, which takes place later than 24 h after immunization. Thus, at least one cell division is required for an immune response in vivo.