Lymphopoiesis and matrix glycoprotein SC1/ECM2.

Rapid progress is being made in characterizing extracellular matrix and other components of the bone marrow microenvironment. New cloning strategies have been particularly helpful in identifying molecules made by marrow stromal cells. Matrix glycoprotein SC1/ECM2 (SC1/ECM2), a calcum-binding secreted protein, is one example and can contribute to the nurturing environment for B lymphocyte precursors. A fusion protein prepared from the SC1/ECM2 and the constant region of human immunoglobulin preferentially bound to B lineage cells in a divalent cation dependent manner. Furthermore, mitogen-dependent proliferation of mature B cells, as well as the cloning of pre-B cells, was increased in a dose dependent manner by addition of the fusion protein. SC1/ECM2 is also capable of augmenting lymphopoiesis when expressed as a transmembrane protein on fibroblasts. While the C-terminal portion of SC1/ECM2 has sequence homology to osteonectin/SPARC, the unique amino-terminal one fifth of the protein was sufficient to augment lymphocyte growth. As additional information accrues about the molecular requirements for lympho-hematopoiesis, it should become possible to engineer more efficient supporting microenvironments.