Production and renewal of murine natural killer cells in the spleen and bone marrow.

The present study was designed to examine the production and renewal patterns of natural killer (NK) cells in mice. NK activity of the marrow and spleen of 4- and 8-wk-old CBA/J mice, respectively, was examined at 24 to 96 hr after repeated administration of hydroxyurea (HU), a cell cycle-specific cytotoxic agent (HU: 1 mg/g body wt twice/day). Newly formed lymphoid cells in both of these organs were eliminated during 96 hr of repeated HU injections as evidenced by the disappearance of cells labeled with concomitant continuous administration of 3H-thymidine in parallel experiments. NK activity measured in a 4-hr 51Cr-release assay, using 51Cr-labeled YAC-1 lymphoma target cells at 5:1 to 50:1 effectontarget ratios, was expressed as a fraction of the activity in control (saline-injected) mice and translated into total NK activity after correction for organ cellularity. Total NK activity of the femoral marrow was unchanged for 10.5 hr after the first HU injection, indicative of the transition time for the DNA-synthesizing NK cell precursor to become an active NK cell. This was followed by an exponential decline with a T½ of 7.9 hr, indicative of rapid exponential renewal of NK cells in the marrow. In the spleen, the total NK activity was unchanged for 20.5 hr, reflecting the total transit time from the last DNA synthesis in the precursors to the appearance of the functional NK cells in this organ, and then declined exponentially with a T½ of 24.75 hr, indicating a rapid and random disappearance of NK cells from the spleen. These findings reveal that although the functional NK cells are not in cell cycle, they belong to a rapidly renewing population derived after a short transition time from their dividing precursors in the bone marrow, wherefrom they leave in a random manner. They also have a short residence time in the spleen, wherefrom they disappear randomly.