In vivo administration of recombinant granulocyte-macrophage colony-stimulating factor results in a reversible inhibition of primary B lymphopoiesis

To determine if in vivo administration of granulocyte-macrophage CSF (GM-CSF) affects production of B lymphocytes in the bone marrow, mice were treated with the cytokine and the kinetics of B cell production was analyzed. After 1 wk of GM-CSF treatment, the number of B cell progenitors that express the B220 Ag had fallen fivefold and surface IgM expressing B cells were barely detectable. Although cellularity in the spleen had increased two-fold, due in part to an increase in the number of granulocyte-macrophage progenitor cells, splenic B cell levels were not affected by the GM-CSF treatment. Although numbers of marrow B cells and their immediate progenitors declined due to cytokine treatment, cells capable of rapidly restoring B lymphopoiesis were present in that tissue. After cessation of GM-CSF treatment, B lymphopoiesis resumed in the marrow of the mice and rebounded to supernormal levels at 1 wk after the last GM-CSF injection. This effect may be due to actions of GM-CSF on the B lymphopoietic support capability of the marrow environment, because the overproduction of B cells was not observed when marrow from the GM-CSF donors was used to reconstitute sublethally irradiated severe combined immunodeficient mice.