Antigen-mediated migration of murine pro-B Ba/F3 cells via an antibody/receptor chimera.
Cell migration is one of the fundamental cellular responses governing development, homeostasis and disorders of the body. Therefore, artificial control of cell migration holds great promise for the treatment of many diseases. In this study, we developed an artificial cell migration system based on chimeric receptors that can respond to an artificial ligand that is quite different from natural chemoattractants. Chimeric receptors consisting of an anti-fluorescein single-chain Fv tethered to the extracellular D2 domain of erythropoietin receptor (EpoR) and the transmembrane/cytoplasmic domains of EpoR, gp130, interleukin-2 receptor, c-Kit, c-Fms, epidermal growth factor receptor (EGFR) or insulin receptor were expressed in the murine Ba/F3 pro-B cell line. Migration assays revealed that chimeric receptors containing the cytoplasmic domain of c-Kit, c-Fms or EGFR transduced migration signals in response to fluorescein-conjugated bovine serum albumin (BSA-FL). Furthermore, based on the cell migration in response to BSA-FL, we successfully selected genetically modified cells from mixtures of gene-transduced and untransduced cells. This study represents the first demonstration of cell migration in response to an artificial ligand that is quite different from natural chemoattractants, suggesting its potential application to immunotherapies and tissue engineering.
Kawahara
Masahiro
M
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. kawahara@bio.t.u-tokyo.ac.jp
Shimo
Yusuke
Y
Sogo
Takahiro
T
Hitomi
Azusa
A
Ueda
Hiroshi
H
Nagamune
Teruyuki
T
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
D000936:Antigen-Antibody Complex; D000941:Antigens; D011947:Receptors, Antigen, B-Cell