Hydroxyurea kills B cell precursors and markedly reduces functional B cell activity in mouse bone marrow.

Hydroxyurea (HU), a cycle-specific drug capable of killing proliferating cells making DNA, was used to study the kinetics of production of pre-B and B cells in the bone marrow and spleen of adult mice. Treatment of mice with two doses of HU separated in time by 7 hr caused marked alterations in the numbers of pre-B and B cells in bone marrow during subsequent days. Immediately after the second dose of HU, the number of B cells in bone marrow is normal. However, the number decreases continuously over the next 6 to 7 days resulting in a 100- to 1000-fold decrease in the number of LPS reactive B lymphocytes in bone marrow. Pre-B cells follow a similar pattern except that they are markedly reduced immediately after the second dose of HU. They also show a continuous further decrease during the next 4 to 5 days resulting in a 100-fold decrease in activity. These decreases in functional activity are mirrored in the slg+ population, which also is reduced 10-fold with respect to the control. These data indicate that the majority of the mitogen-responsive B cells in bone marrow are newly produced. The prolonged decline in activity after a short course of drug indicates that many of the precursors in the B lymphocyte pathway are proliferating the production of B lymphocytes. In addition to pre-B cells that are known to be proliferating cells, it is likely that the progenitors of pre-B cells are also actively proliferating as indicated by the continuous drop in pre-B activity after a single course of drug.