Cross-linking of CD40 using anti-CD40 antibody, 5C11, has different effects on XG2 multiple myeloma cells.
A multiple myeloma (MM) cell line, XG2, has high-level expression of CD40, a tumor necrosis factor receptor (TNFR) family member. CD40 is present on the surfaces of a large variety of cells, including B cells, endothelial cells, dendritic cells and some carcinoma cells, and delivers signals regulating diverse cellular responses, such as proliferation, differentiation, growth suppression, cell death. In this research, we study the effects of cross-linking of CD40 on myeloma cells using different concentrations of anti-CD40 monoclonal antibody (mAb), 5C11. We found that low concentrations of 5C11 induced proliferation of XG2, while high concentrations of 5C11 resulted in homotypic aggregation of XG2, and strongly suppression of its proliferation and apoptosis after 24 h of treatment. These dose-dependent effects of 5C11 were verified by flow cytometry, Western blotting and immunoprecipitation. Autocrine or paracrine induction of IL-6, and up-regulation of membrane TNF and phosphorylation of TNFR1 may partially explain the contradictory biological effects of CD40 cross-linking on XG2 by anti-CD40 mAb.
Qi
Chun-Jian
CJ
Jiangsu Key Laboratory of Clinical Immunology, Institute of Biotechnology, Soochow University, 48 Renmin Road, SuZhou 215007, PR China.
Zheng
Lu
L
Zhou
Xuan
X
Tao
Yi
Y
Ge
Yan
Y
Zhuang
Yu-Mei
YM
Xu
Yin
Y
Yu
GeHua
G
Zhang
Xue-Guang
XG
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D019013:CD40 Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000378:metabolism; D008954:Models, Biological; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D061945:Caspase Inhibitors; D003432:Cross-Linking Reagents; D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha