The influence of cyclophosphamide on antibody formation in the mouse.

A single injection of cyclophosphamide (CY) (300 mg/kg) 8 h prior to immunization results in a complete suppression of the antibody formation in mice. The effect of CY on the number and activity of the surviving cells in the lymphoid organs was studied. For all organs tested there was a decrease in cell numbers to 10% or less till day 3, followed by an increase in cell numbers in bone marrow, spleen and lymph nodes. The increase in cell numbers in the thymus was delayed till after day 11. The bone marrow reached normal levels on day 7. The spleen surpassed the normal levels on day 11, reaching cell numbers which were 50% over the normal ones. For the thymus cells this was found only on day 21. The numbers of lymph node cells remained low and reached normal levels or higher only when the mice were stimulated after CY treatment. This effect of stimulation was further seen in the spleen cell numbers, where after stimulation with antigen in Freund's complete adjuvant (FCA) or only FCA cell numbers of 200% of normal values were obtained. The suppression of antibody formation by CY could be restored by cells from spleen, lymph nodes, Peyer's patches or thymus and bone marrow, indicating a defect in both B and T cells caused by CY treatment. The target cell of CY treatment was studied by reconstitution of anergic mice with spleen or lymph node cells of CY treated mice with or without addition of normal bone marrow and thymus cells. This revealed that although the B cells is the main target cell of CY action, the impact on the T cell population is also considerable. When however CY treatment is followed by antigenic stimulation, there is a steep increase in the activity of the lymph node cells when bone marrow cells are added. This phenomenon resembles the education of thymus cells in the spleen of lethally irradiated mice in the presence of antigen.