PREGNANCY-RELATED STEROIDS ARE POTENTIAL NEGATIVE REGULATORS OF B-LYMPHOPOIESIS

B lymphopoiesis is selectively suppressed in normal pregnant mice, sug gesting that fluctuations in systemic hormone levels might influence l ocal events within bone marrow. This has now been tested by sustained experimental elevation of sex steroids by hormone-containing pellet im plants. We found that while numbers of total nucleated cells declined after treatment with estrone, beta-estradiol, or estriol, there was pr eferential suppression of B-lymphocyte lineage precursors. Progesteron e pellets had no effect when used alone, but mice exposed to progester one were sensitive to several-logarithm lower concentrations of estrog en. Changes in subpopulations of B-lymphocyte lineage cells with hormo ne pellets were similar to those previously recorded in pregnancy. B-l ymphocyte lineage precursors in male and female mice were sensitive to these sex hormones. Acute treatment with single injections of water-s oluble beta-estradiol allowed temporal effects on B-lineage cells to b e documented. With this protocol, total numbers of nucleated cells and myeloid progenitor cells remained unchanged. Interleukin 7-responsive precursors dramatically declined within 1 day of injection, suggestin g that estrogen influences that stage in the B-lymphocyte lineage. The re was a subsequent sharp drop in small pre-B cells 4 days after this transient elevation in estrogen. These experiments demonstrate that B lymphopoiesis is sensitive to negative regulation by sex steroids. The y extend findings made with pregnant animals and parallel previous stu dies of the thymus. Sex steroids might contribute to control of steady -state lymphopoiesis, and fluctuations in their levels could have impl ications for human disease.