Chronic elevation of plasma corticosterone causes reductions in the number of cycling cells of the B lineage in murine bone marrow and induces apoptosis

Steroid-containing implants were used to ascertain the effects of chronic elevation of physiological levels of plasma corticosterone (CS) (30-100 μg/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 B220(bright) IgM⁺ IgD(bright). 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 A(o) 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.