The effect of cyclophosphamide on B cells and 'background' immunoglobulin-secreting cells in mice

The influence of cyclophosphamide (CY) was studied on the B-cell compartment of mice. This was done at five different levels: (a) the serum immunoglobulin (Ig) levels; (b) the numbers of 'background' Ig-secreting cells; (c) the incidence of surface Ig+ B cells; (d) the capacity of lipopolysaccharide-reactive B cells to give rise to a polyclonal IgM- and IgG-response in vitro; and (e) the capacity of long-lived memory B cells to give rise to an adoptive anti-sheep red blood cell plaque-forming cell response in vivo. A single injection of 300 mg CY/kg body weight (BW) decreased the numbers of background IgM-, IgG- and IgA-secreting cells in spleen, bone marrow and lymph nodes to minimum values of about 25% of normal at day 7. The incidence of surface Ig+ B cells also gradually decreased after CY treatment. The functional capacity of the B cells, however, was completely abolished one day after a single injection of 300 mg CY/kg BW. This was found for the lipopolysaccharide-reactive B cells, which largely represent newly formed, short-lived B cells as well as for long-lived memory B cells. The decrease of background Ig-secreting cells following a single injection of 300 mg CY/kg BW was followed by a gradual recovery with a substantial overshoot peaking about 40 days after CY injection. After multiple injections of 100 mg CY/kg BW, the minimum values of background Ig-secreting cells in the various lymphoid organs were lower than after a single injection of 300 mg CY/kg BW, but in this case the recovery was not associated with an overshoot reaction. Remarkably, the serum Ig levels were less profoundly affected than the numbers of Ig-secreting cells in the various lymphoid organs.