Differentiation stage and lineage-specific inhibitor from the stroma of mouse bone marrow that restricts lymphoma cell growth.

We have examined the mechanism by which stromal cells from the microenvironment of the bone marrow restricted the in vitro growth of certain hemopoietic tumors. A series of leukemia cell lines was used to monitor biological activities of stromal cell lines representing five distinct subtypes. Only an endothelial-like clone derived from mouse stroma (MBA-2.1) was consistently found to produce a cell-surface-associated glycoprotein that selectively inhibited the growth of plasmacytomas. The factor, designated leukemia cell inhibitory activity (LCIA), was not detected in anchorage-dependent cells of nonhemopoietic origin. Tumors of the lymphoid lineage and plasmacytomas in particular were the most sensitive to LCIA. Myeloid, macrophage, and erythroleukemia tumors were resistant to the factor, as were normal hemopoietic target cells including pluripotent stem cells, myeloid progenitor cells, and mitogen-stimulated spleen cells. Fractionation of trypsin-released proteins from MBA-2.1 cells by gel filtration and affinity binding to concanavalin A-Sepharose revealed two types of inhibitors; one was the specific leukemia cell inhibitor (i.e., LCIA); the other, present at a lower titer, was non-target-cell specific. The high sensitivity of plasmacytomas to LCIA versus the resistance of normal stem cells may be utilized for selective elimination of plasma cell tumors from bone marrow inocula.