Glucocorticoid-Induced Apoptosis in Early B Cells from Human Bone Marrow

Abstract

The sensitivity of normal human lymphoid precursor cells to glucocorticoid-induced apoptosis is a subject of controversy. The in vitro response of cells of the B lineage (CD19⁺) from the marrow of 22 adult subjects to glucocorticoids was evaluated herein using both natural steroids and dexamethasone (Dex). When exposed to 1 μM Dex, 32% of the subjects exhibited high losses of CD19⁺ B cells in the range of 45%. The remaining subjects exhibited more modest losses in CD19⁺ cells of 26%–40%. Surprisingly, cortisol, a naturally produced glucocorticoid, produced B lineage losses nearly equivalent to Dex, which reached maximum by 12 hr. It was subsequently noted that the variances in losses of CD19⁺ cells among the subjects correlated closely with the proportion of early CD10⁺ CD19⁺ B cells present in the initial population. The latter cells exhibited a high degree of sensitivity to glucocorticoids, with losses of 60%–80% noted. Mature B cells bearing IgD, on the other hand, were fairly resistant to glucocorticoids. Merocyanine 540, a membrane dye that fluoresces in the disordered membrane of apoptotic cells, confirmed that early or progenitor B cells in human bone marrow were indeed undergoing glucocorticoid-induced apoptosis, which could be blocked by the glucocorticoid antagonist RU38486. These data provide evidence that human marrow B cells, especially early B-cell progenitors, are quite sensitive to glucocorticoids and readily undergo apoptosis within a few hours of exposure to the steroids.