title: Apoptosis of multiple myeloma cells induced by agonist monoclonal antibody against human CD28.
abstract: CD28 is expressed abnormally on human multiple myeloma (MM) cells but the significance had not been identified until now. In this paper, we are suggesting that abnormal expression of CD28 might be a marker of tumour progression. We therefore took the approach of generating a hybridoma cell line capable of secreting agonist monoclonal antibody directed against human CD28 (agonist anti-CD28 mAb) and then determined the expression of CD28 molecules on the MM cell lines U266 and XG1. The biological effects of agonist anti-CD28 mAb on cell growth and proliferation of U266 and XG1 cell lines were then analysed. Our results showed that the expression of CD28 on U266 and XG1 was significantly higher than that of PBTC or Jurkat cells. We found that by adding the agonist anti-CD28 mAb to cultures of U266 and XG1 cells their rate of growth and proliferation was obviously inhibited. Further morphological and molecular analyses found that U266 and XG1 incubated with agonist anti-CD28 mAb showed signs of nuclear condensation, chromatin marginal changes, cells membrane breaking, and cytoplasmic shrinkage. Vacuoles and apoptotic bodies were also observed using a transmission electron microscope and the development of typical DNA laddering patterns were found by the use of electrophoresis assays, suggesting that U266 and XG1 cells were undergoing apoptosis induced by agonist anti-CD28 mAb in vitro.
authors.affiliation: Biotechnology Research Institute, Suzhou University, Suzhou 215007, China.
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Qiu
authors.forename: Zhong-wen
authors.initials: ZW
authors.lastname: Sun
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
authors.forename: Cheng-hai
authors.initials: CH
authors.lastname: Su
authors.forename: Yong-jing
authors.initials: YJ
authors.lastname: Chen
authors.forename: Yun-jie
authors.initials: YJ
authors.lastname: Shi
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.forename: Yan
authors.initials: Y
authors.lastname: Ge
authors.forename: Xue-guang
authors.initials: XG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor / Q000502:physiology / Q000648:ultrastructure; D002846:Chromatography, Affinity; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens