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sBAFF mutants induce neutralizing antibodies against BAFF
Author(s) -
Gao Huiguang,
Bian Aina,
Zheng Yingru,
Li Rongfen,
Ji Qing,
Huang Gang,
Hu Daqiang,
Zhang Li,
Gong Wei,
Hu Ying,
He Fengtian
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.12.060
Subject(s) - b cell activating factor , antibody , recombinant dna , epitope , tumor necrosis factor alpha , immune system , biology , b cell , immunology , microbiology and biotechnology , gene , biochemistry
B cell activating factor belonging to the TNF family (BAFF) is a novel member of the tumor necrosis factor (TNF) ligand family and plays an important role in B lymphocyte maturation and survival. Overexpression of BAFF is closely involved in the pathogenesis and progression of many kinds of autoimmune disorders; therefore, BAFF has been considered as an ideal therapeutic target for these conditions. In this study, we generated several candidate immune inhibitors of human BAFF by conjugating foreign immunodominant T‐helper cell (Th) epitopes to the N‐ or C‐terminus of five BAFF mutants. The recombined proteins were successfully expressed in Escherichia coli ( E. coli ) and purified by Ni‐NTA chromatography. BALB/c mice immunized with the recombinant proteins produced high levels of anti‐BAFF antibodies, and their sera inhibited the lymphocyte proliferation‐inducing activity of recombinant soluble BAFF and natural soluble BAFF. Moreover, antibodies cross‐reactive with BAFF were detected in sera from hu‐SCID mice immunized with the recombinant proteins. These results indicated that the recombinant BAFF mutants modified with Th epitopes could induce neutralizing antibodies against BAFF in vivo. This study may provide a valuable strategy for treating BAFF‐associated autoimmune diseases.