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The Proliferative State of Antigen-Sensitive Precursors of Hemolysin-Producing Cells, Determined by the Use of the Inhibitor, Vinblastine

From the Department of Medical Biophysics and Medicine, University of Toronto, and The Ontario Cancer Institute, Toronto, Canada

Abstract

A study has been made of the effects of vinblastine, an inhibitor of cellular proliferation, on the number of hemolysin-producing cells which appear in the spleens of mice following injection of sheep red cells. Vinblastine was given either before, or after, administration of the antigen. When sheep red cells and vinblastine were given in close succession, doses of the inhibitor of greater than 0.1 mg per mouse were found to cause a decrease in the number of hemolysin-producing cells present in the spleen 3–4 days later. A dose of vinblastine of 0.4 mg per mouse produced a 5,000-10,000-fold reduction in the number of hemolysin-producing cells detectable at this time. In contrast, when doses of vinblastine up to 1 mg per mouse were given 3 days prior to injection of antigen, the decrease in numbers of hemolysin-producing cells after 3–4 days was no more than 2-fold, when tested using two different assay procedures.

The results obtained indicate that the precursor cells (antigen-sensitive cells) which respond to antigen by proliferating and giving rise to hemolysin-producing cells, are not proliferating as rapidly in the absence of antigen as in its presence. Thus, an important and early part of the response of these cells to antigen is a change in their state, so that they enter into a more rapid cell cycle.

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