PREGNANCY-RELATED STEROIDS ARE POTENTIAL NEGATIVE REGULATORS OF B-LYMPHOPOIESIS
PREGNANCY-RELATED STEROIDS ARE POTENTIAL NEGATIVE REGULATORS OF B-LYMPHOPOIESIS
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DOI：
10.1073/pnas.91.12.5382
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发表时间：
1994-06-07
影响因子：
11.1
通讯作者：
KINCADE, PW
中科院分区：
文献类型：
--
作者：
MEDINA, KL;KINCADE, PW
正常妊娠小鼠的B淋巴生成被选择性抑制，表明全身激素水平的波动可能影响骨髓内的局部事件。现在已经通过植入含有激素的颗粒来持续提高性类固醇的实验来验证这一点。我们发现，虽然雌酮、β -雌二醇或雌三醇处理后总有核细胞数量下降，但b淋巴细胞谱系前体有优先抑制。孕酮颗粒单独使用时没有效果，但暴露于孕酮的小鼠对低浓度的雌激素敏感。b淋巴细胞谱系细胞亚群的变化与先前在怀孕期间记录的相似。雌雄小鼠b淋巴细胞谱系前体细胞对这些性激素敏感。单次注射水溶性β -雌二醇的急性治疗可以记录对b系细胞的时间效应。在这种方法下，有核细胞和髓系祖细胞的总数保持不变。白细胞介素7反应性前体在注射后1天内急剧下降，表明雌激素影响b淋巴细胞谱系的这一阶段。雌激素短暂升高4天后，小的前b细胞急剧下降。这些实验表明B淋巴生成对性类固醇的负性调节敏感。他们扩展了对怀孕动物的研究结果，并平行于之前对胸腺的研究。性类固醇可能有助于控制稳态淋巴生成，其水平的波动可能对人类疾病有影响。
B lymphopoiesis is selectively suppressed in normal pregnant mice, suggesting that fluctuations in systemic hormone levels might influence local events within bone marrow. This has now been tested by sustained experimental elevation of sex steroids by hormone-containing pellet implants. We found that while numbers of total nucleated cells declined after treatment with estrone, beta-estradiol, or estriol, there was preferential suppression of B-lymphocyte lineage precursors. Progesterone pellets had no effect when used alone, but mice exposed to progesterone were sensitive to several-logarithm lower concentrations of estrogen. Changes in subpopulations of B-lymphocyte lineage cells with hormone pellets were similar to those previously recorded in pregnancy. B-lymphocyte lineage precursors in male and female mice were sensitive to these sex hormones. Acute treatment with single injections of water-soluble beta-estradiol allowed temporal effects on B-lineage cells to be 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, suggesting that estrogen influences that stage in the B-lymphocyte lineage. There 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. They extend findings made with pregnant animals and parallel previous studies of the thymus. Sex steroids might contribute to control of steady-state lymphopoiesis, and fluctuations in their levels could have implications for human disease.