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Matrix Glycoprotein SC1/ECM2 Augments B Lymphopoiesis

Kenji Oritani, Yuzuru Kanakura, Keisuke Aoyama, Takafumi Yokota, Neal G. Copeland, Debra J. Gilbert, Nancy A. Jenkins, Yoshiaki Tomiyama, Yuji Matsuzawa, and Paul W. Kincade

From the Oklahoma Medical Research Foundation, Oklahoma City; the Departments of Internal Medicine II and Hematology/Oncology, Osaka University Medical School, Osaka, Japan; and Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD.

The extracellular matrix produced by stromal cells plays a critical role in lympho-hematopoiesis. It was recently discovered that matrix glycoprotein SC1/ECM2 is a component of that matrix and preliminary evidence suggested that it could contribute to the nurturing environment for B-lymphocyte precursors. A fusion protein prepared from the amino terminal portion of SC1/ECM2 and the constant region of human Ig preferentially bound to pre-B cells. Furthermore, the cloning efficiency of interleukin-7-dependent B-cell precursors was increased in a dose-dependent manner by addition of this fusion protein. We now report the complete cDNA sequence for murine SC1/ECM2 and its localization to the central region of chromosome 5. A fusion protein prepared from the full length of SC1/ECM2 and Ig was found to recognize pre-B cells in a divalent cation-dependent manner, and to augment mitogen-dependent proliferation of mature B cells, as well as the cloning of pre-B cells, but to have no influence on myeloid progenitor cells. Although SC1/ECM2 is normally a secreted protein, we show that it is also capable of augmenting lymphopoiesis when expressed as a transmembrane protein on fibroblasts. Although the C-terminal portion of SC1/ECM2 has sequence homology to osteonectin/SPARC, the unique N-terminal one fifth of the protein was sufficient to augment lymphocyte growth.

Blood, Vol. 90 No. 9 (November 1), 1997: pp. 3404-3413
© 1997 by The American Society of Hematology.


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