Matrix glycoprotein SC1/ECM2 augments B lymphopoiesis.
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.
Oritani
K
K
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Kanakura
Y
Y
Aoyama
K
K
Yokota
T
T
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Tomiyama
Y
Y
Matsuzawa
Y
Y
Kincade
P W
PW
D020410:Activated-Leukocyte Cell Adhesion Molecule; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017154:Stromal Cells / Q000502:physiology
D020410:Activated-Leukocyte Cell Adhesion Molecule; D016326:Extracellular Matrix Proteins; D007136:Immunoglobulins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins