ACTIVATION OF HUMAN B LYMPHOCYTES .4. REGULATORY EFFECTS OF CORTICOSTEROIDS ON TRIGGERING SIGNAL IN PLAQUE-FORMING CELL RESPONSE OF HUMAN PERIPHERAL-BLOOD B LYMPHOCYTES TO POLYCLONAL ACTIVATION

Abstract

In vitro hydrocortisone in physiologic and pharmacologically attainable concentrations caused a marked enhancement of the PWM[pokeweed mitogen]-induced PFC [plaque-forming cell] response of normal human peripheral blood B [bone marrow-derived] lymphocytes. This effect was seen only when hydrocortisone was added within the first 24 h of culture and only when hydrocortisone and PWM were present together in cultures. Only suprapharmacologic concentrations of hydrocortisone (10-3 M) were capable of suppressing early B cell activation. Late stages of antibody production and secretion were resistant to suppression by even these extraordinarily high concentrations. Hydrocortisone did not replace the T [thymus-derived] cell requirement of PWM-induced PFC responses. A single dose of in vivo hydrocortisone (400 mg) to normal adult volunteers did not produce this enhancing effect when PFC responses were measured in vitro in the absence of hydrocortisone. The enhancing effect of hydrocortisone was probably not due to elimination of naturally occurring suppressor cells, but to a modulation of the triggering signal directly on the B cell itself or via the balance of positive and negative T cell regulation of B cell activation.