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 chro nic elevation of physiological levels of plasma corticosterone (CS) (3 0-100 mu g/dl) on lymphopoietic processes in the bone marrow of the mo use. Phenotypic analysis of bone marrow B-lineage lymphocytes using fl ow cytometry (FACS) indicated a 50% decrease in bone marrow Ig(+) cell s, and a 70-80% decrease in B220(+) cells had occurred 3 days after ex posure 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 r emaining 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 c ycle declined 75% after 24 hr exposure to CS. A few hours after CS imp lantation, the appearance of a small but distinct population of B220() and IgM(+) cells in the 'hypodiploid' region of the cell cycle was a lso noted, which was previously termed the A(0) region and corresponde d to cells undergoing apoptosis. Thus, the chronic presence of modestl y elevated levels of plasma CS analogous to that produced during malnu trition, stress and trauma caused rapid depletion of developing B-line age cells in the marrow by reducing the number of cycling precursor B cells and inducing apoptosis.