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Blood, 12 February 2009, Vol. 113, No. 7, pp. 1422-1431. Prepublished online as a Blood First Edition Paper on December 4, 2008; DOI 10.1182/blood-2008-09-177139. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-09-177139v1 113/7/1422    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Luo, X. M. Articles by Baltimore, D. Search for Related Content PubMed PubMed Citation Articles by Luo, X. M. Articles by Baltimore, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 8, 2008 Accepted November 20, 2008 Engineering human hematopoietic stem/progenitor cells to produce a broadly neutralizing anti-HIV antibody after in vitro maturation to human B lymphocytes Xin M. Luo, Emily Maarschalk, Ryan M. O'Connell, Pin Wang, Lili Yang, and David Baltimore* Division of Biology, California Institute of Technology, Pasadena, CA, United States Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, United States * Corresponding author; email: baltimo{at}caltech.edu. Broadly neutralizing anti-HIV antibodies are rare and have proved hard to elicit with any immunogen. We have tested in vitro the notion that such antibodies or other anti-viral proteins could be made by lentivirus-mediated gene transfer into human hematopoietic stem/progenitor cells (HSPCs), followed by differentiation of the transduced cells into B cells, the most potent antibody-producing cells. To do this, we have developed a highly efficient system for in vitro maturation of secreting B lymphocytes and plasma cells from CD34+ HSPCs. It is a three-stage, in vitro culture system that supports normal human B-lineage development from HSPCs to antibody-secreting plasmablasts (~36%) and plasma cells (~20%). By transducing human cord blood CD34+ cells with lentiviral vectors encoding a secretory monoclonal anti-HIV antibody, b12 (IgG1), we were able to program human B cells to produce in vitro up to 1.5 µg/mL of this broadly neutralizing antibody. Our results suggest that an HIV vaccine might be delivered by autologous transplantation of in vitro-programmed HSPCs, which would develop into antibody-secreting B cells in vivo and provide a continuous supply of anti-HIV neutralizing antibodies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Xue, X. Huang, S. E. Nodland, L. Mates, L. Ma, Z. Izsvak, Z. Ivics, T. W. LeBien, R. S. McIvor, J. E. Wagner, et al. Stable gene transfer and expression in cord blood-derived CD34+ hematopoietic stem and progenitor cells by a hyperactive Sleeping Beauty transposon system Blood, August 13, 2009; 114(7): 1319 - 1330. [Abstract] [Full Text] [PDF]

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