Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1996-05-22
1999-06-22
Mertz, Prema
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
435 712, 4352523, 4353201, 435325, 435471, 536 235, 536 2431, 530351, C07K 1452, C12N 1519, C12N 1563, C12N 510
Patent
active
059142529
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a gene and a novel membrane protein encoded by said gene, and more specifically, relates to a gene encoding a novel membrane protein polypeptide having pre-B cell growth-supporting ability, a vector containing said gene, transformants transformed by said vector and a method for producing the novel membrane protein polypeptide by using said gene.
The present invention further relates to a monoclonal antibody recognizing a novel membrane protein polypeptide having pre-B cell growth-supporting ability.
The gene of the present invention encodes a novel membrane protein polypeptide enhancing pre-B cell growth-supporting ability on the surface of synovial cells derived from patients with rheumatoid arthritis (RA). In the present invention, a homogeneous and purified novel membrane protein polypeptide having pre-B cell growth-supporting ability can be produced in large quantities by transforming appropriate host cells with a suitable vector in which the gene of the present invention is inserted. Thus, according to the present invention, it becomes possible to identify rheumatoid arthritis (RA), and also prepare reagents for the clinical diagnosis thereof.
BACKGROUND ART
Inflammatory cells in the synovial membrane and the synovial fluid of patients with rheumatoid arthritis (RA) are derived from peripheral blood and the migration of these cells to synovial membranes has not been explicated perfectly yet, but it is believed to be caused by a complicated interaction between chemical signals given to cells and protein (adhesion molecule) on cell membranes.
Various studies upon the significance of membrane proteins in arthritis have been performed. For example, it is known that an intercellular adhesion molecule-1 (hereinafter referred to as ICAM-1)is expressed on the inner layer of the synovial membrane and the blood vessel of the synovial membrane of patients with rheumatoid arthritis (RA), which is a ligand of a T cell surface molecule LFA-1 and causes both adhesion and migration of (1989), and Hayes et al.; Springer Semin. Immunopathol., 11:163 (1989)!.
Similarly, it is suggested that a vasocellular adhesion molecule-1 (hereinafter referred to as VCAM-1), which is a ligand of intergrin VLA-4 expressed on T lymphoid cells (memory cells in particular) and monocytes, is expressed on the synovial membrane and fibroblast-like synovial cells J. Immunol., 149:1424 (1992)!, and further that a membrane protein called VAP-1 is expressed on the endothelial vein of a synovial membrane and may Science, 257, 1407 (1992)!.
The present inventors have engaged in extensive studies with a view to investigating the function of the bone marrow microenvironments in disorders causing abnormalities of B cells, and have found that the pre-B cell growth-supporting ability of bone marrow stromal cells derived from patients with rheumatoid arthritis (RA) and multiple myeloma (MM) is enhanced in comparison with that of healthy donor-derived bone marrow stromal cells and that the direct contact of pre-B cells with stromal cells might play an essential role in this supporting ability. And the present inventors have established novel stromal cell lines (RASV5-5, MMSV3-3) containing a molecule enhancing the growth of pre-B cells by cell-lining stromal cells of patients, and have found that the pre-B cell growth-supporting activity of these stromal cell lines is most likely caused by unknown adhesion molecules different from known stem cell factors (SCF), ICAM, CD44, VCAM-1, LFA-1.alpha., LFA-1.beta., NCAM and
Further, since it has been suggested that the synovial cell line SynSV6-14 established from the synovial cell derived from patients with rheumatoid arthritis (RA) has pre-B cell growth-supporting ability similarly to the stromal cell line RASV5-5 derived from the bone marrow of patients with rheumatoid arthritis (RA), the present inventors have obtained a novel monoclonal antibody which responds to these cell lines but does not respond to the stromal cell line NFSV1-1 derived from the huma
REFERENCES:
Cunningham et al. Science, vol. 244, pp. 1081-1085, 1989.
George et al. Macromolecular Sequencing and Synthesis, Ch. 12, pp. 127-149, 1988.
Hirano et al. Nature, vol. 324, pp. 73-76, 1986.
Ishikawa et al., Genomics, vol. 26, pp. 527-534, 1995.
Hirano Toshio
Kaisho Tsuneyasu
Hirano Toshio
Mertz Prema
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