BAFF, inhibitors thereof and their use in the modulation of B-cell response and treatment of autoimmune disorders

Abstract

The invention provides methods for treating or preventing disorders associated with expression of BAFF comprising BAFF and fragments thereof, antibodies, agonists and antagonists.

1 - 59 . (canceled)  
     
     
         60 . A method of treating a mammal, the method comprising administering to a mammal having Sjögren's syndrome a composition comprising a BAFF blocking agent, thereby reducing immunoglobulin production or B cell growth in the mammal.  
     
     
         61 . The method of  claim 60 , wherein the mammal is a human.  
     
     
         62 . The method of  claim 60 , wherein the mammal is a mouse.  
     
     
         63 . The method of  claim 62 , wherein the mouse is a BAFF Tg mouse.  
     
     
         64 . The method of  claim 60 , wherein the salivary gland of the mammal is infiltrated by MZ-like B cells.  
     
     
         65 . The method of  claim 60 , wherein the BAFF blocking is selected form the group consisting of: 
 (a) a soluble BAFF receptor;    (b) an antibody against BAFF ligand;    (c) an antibody against BAFF receptor; and    (d) an inoperative BAFF ligand molecule.    
     
     
         66 . The method of  claim 65 , wherein soluble BAFF receptor comprises an immunoglobulin Fc domain.  
     
     
         67 . The method of  claim 65 , wherein the BAFF receptor is BAFF-R.  
     
     
         68 . The method of  claim 65 , wherein the BAFF receptor is TACI.  
     
     
         69 . The method of  claim 65 , wherein the BAFF receptor is BCMA.  
     
     
         70 . The method of  claim 67 , wherein BAFF-R is human.  
     
     
         71 . The method of  claim 65 , wherein the soluble BAFF receptor comprises a portion of SEQ ID NO:27 that binds to BAFF.  
     
     
         72 . The method of  claim 71 , wherein the soluble BAFF receptor further comprises a human immunoglobulin Fc domain.  
     
     
         73 . The method of  claim 67 , wherein BAFF-R is murine.  
     
     
         74 . The method of  claim 70 , wherein the soluble BAFF receptor comprises a portion of SEQ ID NO:28 that binds to BAFF.  
     
     
         75 . The method of  claim 65 , wherein the antibody against BAFF ligand or BAFF receptor is a monoclonal antibody.  
     
     
         76 . The method of  claim 75 , wherein the antibody is recombinantly produced.  
     
     
         77 . The method of  claim 75 , wherein the antibody is a chimeric antibody.  
     
     
         78 . The method of  claim 75 , wherein the antibody is a humanized antibody.  
     
     
         79 . The method of  claim 75 , wherein the antibody comprises human constant domains.  
     
     
         80 . The method of  claim 75 , wherein the antibody is a F(ab′)2 fragment.  
     
     
         81 . The method of  claim 60 , further comprising detecting the level of B cell growth in the mammal.  
     
     
         82 . The method of  claim 60 , further comprising detecting the level of immunoglobulin production in the mammal.  
     
     
         83 . The method of  claim 60 , further comprising detecting the levels of B cell growth and immunoglobulin production in the mammal.  
     
     
         84 . The method of  claim 60 , further comprising detecting circulating levels of a rheumatoid factor in the mammal.  
     
     
         85 . The method of  claim 60 , further comprising detecting circulating levels of anti-DNA autoantibody in the mammal.