Suppression of the antigenic response of murine bone marrow B cells by physiological concentrations of glucocorticoids

Abstract

Data presented here indicate that the immature B cells of murine bone marrow (BM) may be as sensitive to glucocorticoids (GC) as are immature thymocytes, since physiological levels of the steroids significantly inhibited the response of these cells to trinitrophenylated lipopolysaccharide (TNP-LPS) in short-term culture. The in vitro response of B cells of the marrow to TNP-LPS was reduced more than 50% by concentrations of corticosterone and cortisol analogous to that found in plasma during stress and trauma. The more potent synthetic GC, dexamethasone (DX), caused a 50-80% decrease in plaque-producing cells at concentrations of 10(-6) and 10(-8) M. The same pattern of inhibition was noticed regardless of whether DX was added 24 hr prior or up to 48 hr after addition of antigen to culture. However, no inhibition in the response of B cells was noted when DX was added 72-96 hr after stimulation of the cultures. These effects were found to be specific for GC since neither testosterone nor progesterone at physiological concentrations inhibited the response, while the glucocorticoid receptor antagonist RU 38486 provided protection. A greater than 80% reduction in the proportion of B cells present in the DX-treated cultures was noted after 5 days, corresponding to the 80% inhibition of plaque-forming cell production observed at that time. This reduction in B cells was rapid since almost 40% of the B220+ cells were depleted within 12 hr of DX addition. These data indicate that physiological levels of GC can readily inhibit the capacity of BM to respond to antigen by depleting the cultures of immature B cells.