Soluble receptor br43x2 and methods of using

Abstract

Soluble, secreted tumor necrosis factor receptor polypeptides, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed. The polypeptides comprise one cysteine-rich repeat that is homologous to other tumor necrosis factor receptors, such as transmembrane activator and CAML-interactor (TACI). The polypeptides may be used for detecting ligands, agonists and antagonists. The polypeptides may also be used in methods that modulate B cell activation.

1 . A method of inhibiting B lymphocyte proliferation in a mammal, comprising administering to the mammal a composition comprising a fusion protein consisting of a first portion and a second portion, wherein the first portion and second portion are joined by a peptide bond, wherein the first portion of the fusion protein consists of a ztnf4-binding fragment of the transmembrane activator and calcium-modulator and cyclophilin ligand-interactor (TACI) extracellular domain comprising the sequence of SEQ ID NO: 10, wherein the second portion of the fusion protein comprises an immunoglobulin heavy chain constant region, and wherein the fusion protein binds ztnf4. 
     
     
         2 . The method of  claim 1 , wherein the ztnf4-binding fragment of the TACI extracellular domain comprises amino acid residues 34-66 of SEQ ID NO: 6. 
     
     
         3 . The method of  claim 1 , wherein the ztnf4-binding fragment of the TACI extracellular domain comprises amino acid residues 71-104 of SEQ ID NO: 6. 
     
     
         4 . The method of  claim 1 , wherein the immunoglobulin heavy chain constant region is a human immunoglobulin heavy chain constant region. 
     
     
         5 . The method of  claim 4 , wherein the human immunoglobulin heavy chain constant region is a human immunoglobulin heavy chain constant region of IgG1. 
     
     
         6 . The method of  claim 1 , wherein the composition comprises multimeric proteins comprising one or more polypeptide fusions. 
     
     
         7 . The method of  claim 6 , wherein the composition comprises dimeric proteins comprising one or more polypeptide fusions. 
     
     
         8 . The method of  claim 1 , wherein said B lymphocyte proliferation is associated with an autoimmune disease. 
     
     
         9 . The method of  claim 8 , wherein said autoimmune disease is systemic lupus erythematosus, myasthenia gravis, multiple sclerosis, insulin dependent diabetes mellitus or rheumatoid arthritis. 
     
     
         10 . The method of  claim 1 , wherein said B lymphocyte proliferation is associated with asthma, bronchitis, emphysema, Crohn's Disease, or end stage renal failure. 
     
     
         11 . The method of  claim 1 , wherein said B lymphocyte proliferation is associated with renal disease. 
     
     
         12 . The method of  claim 11 , wherein said renal disease is glomerulonephritis, vasculitis, nephritis or pyelonephritis. 
     
     
         13 . The method of  claim 1 , wherein said B lymphocyte proliferation is associated with renal neoplasms, multiple myelomas, lymphomas, light chain neuropathy or amyloidosis. 
     
     
         14 . The method of  claim 1 , wherein said lymphocyte proliferation is associated with regulating immune response. 
     
     
         15 . The method of  claim 1 , wherein said B lymphocyte proliferation is associated with graft rejection, graft versus host disease, or inflammation. 
     
     
         16 . The method of  claim 15 , wherein said inflammation is associated with joint pain, swelling, anemia or septic shock.