Autoinduction of differentiation in WEHI-3B leukemia cells.

Cells of the differentiation-responsive mouse myelomonocytic leukemia cell line WEHI-3B D+ form colonies in agar exhibiting a low frequency of spontaneous differentiation mainly in the macrophage pathway. Compared with undifferentiated colonies, spontaneously differentiating colonies have a reduced content of clonogenic cells and surviving clonogenic cells tend themselves to form differentiating colonies, both being characteristics of differentiated colonies induced by the regulator, granulocyte colony-stimulating factor, G-CSF. Colony crowding increased the frequency of spontaneously differentiating colonies and WEHI-3B D+ colony cells were shown to release material able to induce differentiation in WEHI-3B D+ colonies. Cells from spontaneously differentiating D+ colonies were not hyperresponsive to the induction of differentiation by G-CSF and did not release larger amounts of differentiation-inducing material than did cells from undifferentiated colonies. Cells of the differentiation-unresponsive WEHI-3B D-line produced similar amounts of differentiation-inducing material to those produced by D+ cells. Apparently spontaneous differentiation in WEHI-3B D+ colonies seems most likely to be due to exposure of the colony-forming cell or its ancestors to a differentiation-inducing factor of WEHI-3B origin prior to culture in agar, the genetic program initiating differentiation being inherited by the progeny of the exposed cell.