Garvy B A, King L E, Telford W G, Morford L A, Fraker P J
Department of Biochemistry, Michigan State University, E. Lansing 48824.
Immunology. 1993 Dec;80(4):587-92.
Steroid-containing implants were used to ascertain the effects of chronic elevation of physiological levels of plasma corticosterone (CS) (30-100 micrograms/dl) on lymphopoietic processes in the bone marrow of the mouse. Phenotypic analysis of bone marrow B-lineage lymphocytes using flow cytometry (FACS) indicated a 50% decrease in bone marrow Ig+ cells, and a 70-80% decrease in B220+ cells had occurred 3 days after exposure to steroid. By day 5, the B220+ Ig- precursor B cells in the marrow of mice exposed to CS were nearly depleted, with many of the remaining B cells being B220bright IgM+IgDbright. To determine if the depletion of B cells was due to disruption in cell cycling and/or induction of apoptosis, phenotype-gated FACS cell cycle analysis was utilized. The proportion of B220+ cells in the S phase of the cell cycle declined 75% after 24 hr exposure to CS. A few hours after CS implantation, the appearance of a small but distinct population of B220+ and IgM+ cells in the 'hypodiploid' region of the cell cycle was also noted, which was previously termed the Ao region and corresponded to cells undergoing apoptosis. Thus, the chronic presence of modestly elevated levels of plasma CS analogous to that produced during malnutrition, stress and trauma caused rapid depletion of developing B-lineage cells in the marrow by reducing the number of cycling precursor B cells and inducing apoptosis.
使用含类固醇的植入物来确定血浆皮质酮（CS）生理水平长期升高（30 - 100微克/分升）对小鼠骨髓中淋巴细胞生成过程的影响。使用流式细胞术（FACS）对骨髓B系淋巴细胞进行表型分析表明，暴露于类固醇3天后，骨髓Ig⁺细胞减少了50%，B220⁺细胞减少了70 - 80%。到第5天，暴露于CS的小鼠骨髓中B220⁺ Ig⁻前体B细胞几乎耗尽，剩余的许多B细胞为B220bright IgM⁺IgDbright。为了确定B细胞的耗竭是否是由于细胞周期紊乱和/或凋亡诱导，采用了表型门控FACS细胞周期分析。暴露于CS 24小时后，细胞周期S期的B220⁺细胞比例下降了75%。在CS植入后数小时，还注意到在细胞周期的“亚二倍体”区域出现了一小群但明显的B220⁺和IgM⁺细胞，该区域先前被称为Ao区域，对应于正在经历凋亡的细胞。因此，与营养不良、应激和创伤期间产生的水平类似的适度升高的血浆CS的长期存在，通过减少循环前体B细胞的数量并诱导凋亡，导致骨髓中正在发育的B系细胞迅速耗竭。
