Human bone marrow lymphocytes. Cytotoxic effector cells in the bone marrow of normal individuals.

Abstract

A B S T R A C T This study was undertaken to determine the capability of lymphocytes in the bone marrow of normal individuals to mediate nonspecific killer cell functions in assays of phytohemagglutinin (PHA) -induced cellular cytotoxicity, and antibody-dependent cellular cytotoxicity (ADCC) against "1Cr-labeled chicken erythrocyte target cells. Relatively pure mononuclear cell suspensions were obtained from bone marrow aspirates in 30 normal volunteers by sucrose gradient centrifugations and from the peripheral blood of the same individuals by Hypaque-Ficoll density centrifugations. At an effector: target ratio of 10: 1, the PHA-induced cellular cytotoxicity of peripheral blood was 78.8±1.3%, while that of bone marrow was not significantly less at 66+9% (P > 0.1). At low effector: target ratios, the ADCC of bone marrow was negligible, while at higher effector: target ratios (20: 1) bone marrow ADCC was 69±3.7%, which was comparable to that of peripheral blood. The lymphocytes themselves in the mononuclear cell suspensions of both peripheral blood and bone marrow were capable of cytotoxic activity since depletion of monocytes from the suspensions by adherence to rayon wool and G-10 Sephadex columns did not remove the cytotoxic activity. Blocking of the Fc receptor on the effector cells by the addition of aggregated gamma globulin to the cultures suppressed the ADCC but not the PHA-induced cellular cytotoxicity of both peripheral blood and bone marrow, indicating that ADCC is dependent on an Fc receptor on the effector cell in both compartments. These studies demonstrate that the bone marrow of normal humans contains populations of lymphoid cells which have highly efficient killer cell capacities. It is uncertain what portion

Polyclonally triggered B cells in the peripheral blood and bone marrow of normal individuals and in patients with systemic lupus erythematosus and primary sjögren's syndrome

“…However, of particular importance was the almost 20-fold increase in PFC in simultaneously assayed bone marrow from the same normal individuals. We (27)(28)(29) and others (26,37) have previously stressed that in humans, the bone marrow is an important source of lymphocytes, particularly B cells. However, the increased numbers of Ig-secreting cells in bone marrow cannot be explained merely by the presence of a greater proportion of B cells, since the proportion of cells with detectable B cell surface markers relative to total mononuclear cells is approximately the same in human peripheral blood and bone marrow (27,37).…”

“…Bone marrow aspirates and peripheral blood suspensions. Bone marrow aspirates of 2 to 3 ml were obtained in heparinized plastic syringes from the posterior superior iliac crest as previously described in detail (27)(28)(29). The relative proportion of peripheral blood lymphocytes contaminating bone marrow lymphoid cells in such aspirates is minimal and has previously been discussed in detail (27)(28)(29).…”

“…Bone marrow aspirates of 2 to 3 ml were obtained in heparinized plastic syringes from the posterior superior iliac crest as previously described in detail (27)(28)(29). The relative proportion of peripheral blood lymphocytes contaminating bone marrow lymphoid cells in such aspirates is minimal and has previously been discussed in detail (27)(28)(29). Immediately prior to obtaining the bone marrow aspirate, 60 ml of heparinized venous blood was drawn and with each individual, bone marrow and blood specimens were subsequently assayed simultaneously.…”

“…In previous studies on human bone marrow lymphocytes (27)(28)(29), purified mononuclear cells were obtained from the bone marrow aspirates by a sucrose density gradient centrifugation method. In those studies, only mononuclear cells were assayed and not the entire bone marrow leukocyte suspension.…”

“…Since activated and antibody-secreting cells not found in the peripheral blood may be sequestered in other organs, it was possible that the triggered B cells in Sjogren's syndrome were not circulating, but were sequestered. The bone marrow contains large numbers of B cells in both animals and humans (26)(27)(28)(29). Since the bone marrow can serve as both a source of B cells in humans and a potential site of B cell sequestration, the present study examined the relative levels of B cell activation simultaneously in the peripheral blood and bone marrow of patients with SLE compared to patients with Sjogren's syndrome in order to determine: l) the relationship, if any, between polyclonally activated B cells in the blood and bone marrow and 2) the possibility that activated B cells are sequestered in the bone marrow of patients with Sjogren's syndrome.…”