902 MONOCYTE SUPPRESSION OF IMMUNOGLOBULIN SECRETION IN A 9-YEAR-OLD BOY WITH SCID

Abstract

We report the evaluation of in vitro immunoregulation in a 9-year-old untreated boy with SCID. Ficoll-Hypaque-isolated peripheral blood mononuclear cells (MNL) from the patient failed to respond to pokeweed mitogen (PWM) with the normal increment in immunoglobulin-secreting cells (Ig-SC), as measured by a reverse hemolytic plaque assay. Removal of phagocytic cells or the addition of unrelated irradiated helper cells resulted in enhanced, but still suboptimal response to PWM, suggesting some intrinsic defect in B-cell function. Co-culture of patient with normal MNL resulted in marked (88%) suppression of PWM-induced Ig-SC. Suppressor activity was unaffected by prior irradiation of patient MNL, but was substantially reversed (32% net enhancement) by removal of his phagocytic cells; whereas the combination of the two procedures further reversed suppression (52% net enhancement). Because the patient was lymphopenic, his MNL were relatively enriched for monocytes (range=40-80%). To determine whether the suppressor cell activity was due to functional or numerical excess of patient monocytes, co-cultures were performed using varying ratios of patient to normal MNL. Suppression was most marked in cultures containing >40% monocytes, suggesting that a numerical excess of patient monocytes could account for the observed suppression. These data suggest both an intrinsic defect in B-cell function, and a relative numerical excess of monocytes which could further inhibit Ig-secretion by B-cells.