Regulation of natural killer cell production in bone marrow of mice: no evidence for negative feedback control

The possible presence of a negative feedback control mechanism regulating natural killer (NK) cell production in the bone marrow of B6 mice was investigated by depleting NK cells with a single intravenous injection of anti-ASGM1 antibody. At times ranging from 1 to 21 days following injection, the response of the bone marrow cells to this depletion was assessed by measuring both NK activity against YAC-1 target cells in a 51Cr assay and the frequency of NK precursors by limiting dilution analysis. For comparison, measurements of lytic activity were also done in the peripheral blood and spleen. Anti-ASGM1 injection resulted in a depletion of mature NK cell activity in all compartments tested as expected, as well as the depletion of NK precursors from the bone marrow. Clearance of the anti-ASGM1 from the circulation of recipient mice was biphasic. More than 99% of the antibody was eliminated in the first 4 min, while the remaining 0.24% had a half-life in the serum of 6 days. Bone marrow was able to produce new lytic NK cells which were detectable between days 6 and 10 after depletion. The bone marrow of the NK cell-depleted mice did not show an 'overshoot' (compensatory increase) in NK cell production through day 21 after depletion. It therefore appears that the NK cell production in the bone marrow is independent of the activity of the peripheral NK cell pool.