Preparation And Characterization Of Monoclonal Antibody Against TACI

The number of tumor necrosis factor superfamily(TNFSF) and tumor necrosis factor receptor superfamily(TNFRSF) has been extremely expanded since large-scale sequencing of "expressed sequence tags(ESTs)" and Bioinformatics have been used.They can not only integrate mammalian biology, but also have correlation with many diseases. Transmembrane activator and calcium modulator and cyclophilin ligand(CAML) interactor(TACI) is a novel member of TNFRSF, which interacts with two ligands,B lymphocyte stimulator (BlyS, also called BAFF) and a proliferation inducing ligand(APRIL),modulating humoral and cellular immunity.B cell maturation molecule(BCMA),another new member of TNFRSF, may compete the binding of TACI with its ligands. Recently,it was found that BAFFR is a specific receptor for BAFF.TACI belongs to type I transmembrane protein,which expressed on mature B cells and activated T cells. In the mouse model of collagen II -induced rheumatoid arthritis(RA), TACI-Fc could prevent the binding of Blys and APRIL with TACI and/or BCMA, consequently inhibit humoral and cellular immunity,and reduce the pathological changes of rheumatoid arthritis.BlyS transgenic mice cause B cell accumulation and activation, secretion of anti DNA antibody and other autoantibodies (such as RF), and develop the symptom of autoimmune nephritis. TACI-Fc may block B cell proliferation and T cell activation in vitro, decrease the number of B cells, inhibit the generation of germinal center(GC) and alleviate symptoms of nephritis in vivo, and increase the survival rate,suggesting that soluble TACI may have the therapeutic function by interfering the secretion of autoantibodies, and show favorable development prospect. The preparation and characterization of anti TACI monoclonal antibodies will provide important tools in research of the relationship of structure and functions of TACI molecule and the mechanisms of autoimmune diseases.McAbs E3.5 and E3.7 were raised by B lymphocyte hybridoma technique.We found that the molecule recognized by two mAbs is expressed on both CD4+ and CD8+ T lymphocytes activated by alloantigen, PHA and PMA.Moreover, we found that E3.5 could recognize the molecule expressed on derma of skin of 38wk-fetus and the germinal center of tonsil tissue by immunohistochemical assay.