Construction and function of two Cys146-mutants with high activity, derived from recombinant human soluble B lymphocyte stimulator.
B lymphocyte stimulator (BLyS) is a novel member of tumor necrosis factor (TNF) ligand family that is important in B cell maturation and survival. Previous studies were almost related to the function or mechanism of its wild type. Here, we constructed two site-directed mutants of the recombinant human soluble BLyS, the BY-A and BY-V, and found that BY-V ranked the highest whenever in the process of promoting proliferation of B lymphocytes in vitro or stimulating total serum IgG and IgM secretion in vivo. Besides, assays for the biological responses of human leukemic cell lines to BLyS, BY-A and BY-V demonstrated that they could suppress the proliferation of Raji cells but promote the growth of THP-1. The discovery of BY-V with high activity will help come to a conclusion that the mutation of Cys146 to Val146 might improve the biological activity of BLyS.
Laboratory of Molecular Genetics, Beijing Institute of Basic Medical Sciences, Beijing, China 100850.
Guangyu
G
Chen
Shanyun
S
Peng
Minji
M
Zou
Honglian
H
Xu
Donggang
D
Xu
Jiaxi
J
Wang
D053264:B-Cell Activating Factor; D003545:Cysteine / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M; D007938:Leukemia / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D011994:Recombinant Proteins / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008565:Membrane Proteins; D011994:Recombinant Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D003545:Cysteine