Natural suppressor (NS) activity is detected in tissues undergoing intense hematopoietic regeneration. This includes the spleens of mice recovering from total lymphoid irradiation or cyclophosphamide treatment, or after induction of chronic graft-versus-host disease against minor histocompatibility antigens. NS cells are thought to act via an antiproliferative mechanism, based on the observation that NS cells inhibit thymidine ([3H]TdR) uptake by mitogen- or antigen-activated lymphocytes. In the present study, the mechanism of B cell inhibition by NS activity present in normal adult bone marrow is analyzed. [3H]TdR uptake of LPS-stimulated B cells is inhibited by the presence of bone marrow cells (BMC). Consistent with the decrease in DNA synthesis, cell cycle analysis reveals that the majority of B cells fail to exit G0. To determine whether cells in G1 are also susceptible to inhibition by BMC, we tested the ability of cells with NS activity to inhibit the LPS response of either low-density B cells or B cells preactivated by LPS. Both populations of cells were readily inhibited in their uptake of [3H]TdR. Direct analysis of B cell growth in suppressed cultures demonstrates that B cell numbers remain constant, with only 630% of the control number of B cells present in cultures containing BMC. Taken together, these results indicate that the antiproliferative effect of NS cells is a result of not only resting B cells being inhibited from entering the cell cycle, but also the inhibition of B cells already in G1.
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