conditional immortalization of human b cells by cd40 ligation有条件的不灭的人类b细胞cd40结扎.pdfVIP

Conditional Immortalization of Human B Cells by CD40 Ligation 1.¤a 1. 2¤b 3 4 5 Martina Wiesner , Caroline Zentz , Christine Mayr , Rainer Wimmer , Wolfgang Hammerschmidt , Reinhard Zeidler , Andreas Moosmann1* ¨ 1 Clinical Cooperative Group Molecular Oncology, GSF - National Research Center and Ludwig-Maximilians-Universitat, Munich, Germany, 2 Institute ¨ ¨ for Human Genetics, Technische Universitat, Munich, Germany, 3 Institute for Human Genetics, Ludwig-Maximilians-Universitat, Munich, Germany, 4 Department of Gene Vectors, GSF - National Research Center for Environment and Health, Munich, Germany, 5 Department of Otorhinolaryngology, ¨ Ludwig-Maximilians-Universitat, Munich, Germany It is generally assumed that human differentiated cells have a limited life-span and proliferation capacity in vivo, and that genetic modifications are a prerequisite for their immortalization in vitro. Here we readdress this issue, studying the long-term proliferation potential of human B cells. It was shown earlier that human B cells from peripheral blood of healthy donors can be efficiently induced to proliferate for up to ten weeks in vitro by stimulating their receptor CD40 in the presence of interleukin-4. When we applied the same stimuli under conditions of modified cell number and culture size, we were surprised to find that our treatment induced B cells to proliferate throughout an observation period of presently up to 1650 days, representing more than 370 p