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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1611-1619. Prepublished online as a Blood First Edition Paper on October 10, 2006; DOI 10.1182/blood-2006-03-008441. This Article Full Text (PDF) All Versions of this Article: blood-2006-03-008441v1 109/4/1611    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 Huggins, J. Articles by Zand, M. S. Search for Related Content PubMed PubMed Citation Articles by Huggins, J. Articles by Zand, M. S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 15, 2006 Accepted September 19, 2006 CpG DNA activation and plasma cell differentiation of CD27- naive human B cells Jennifer Huggins, Tina Pellegrin, Raymond E. Felgar, Chungwen Wei, Miguel Brown, Bo Zheng, Eric C.B. Milner, Steven H. Bernstein, Ignacio Sanz, and Martin S. Zand* University of Rochester Medical Center * Corresponding author; email: martin_zand{at}urmc.rochester.edu. Unmethylated CpG DNA activation of naive CD27- B cells has been reported to require B cell receptor (BCR) cross-linking. We describe a culture system using CpG DNA with sequential steps for T cell independent activation of naive CD19+CD27- human peripheral blood B cells that induces efficient CD138+ plasma cell differentiation. CD27+ and CD27- Cells were cultured in a three step system: (1) Day 0-4: CpG + IL-2/10/15; (2) Day 4-7: IL-2/6/10/15 + anti-CD40L; (3) Day 7-10: IL-6/15, IFN-, hepatocyte growth factor, and hyaluronic acid. Both CD27+ and CD27- B cells up-regulated intracytoplasmic TLR-9 following CpG DNA activation. CD27- B cell activation required cell-cell contact. Both naive and memory B cells progressed to a plasma cell phenotype: CD19lowCD20lowCD27+CD38+HLA-DRlow. 70% of the CD27- derived CD138+ cells demonstrated productive V chain rearrangements without somatic mutations, confirming their origin from naive precursors. Plasma cells derived from CD27+ B cells were primarily IgG+ while those from CD27- B cells were IgM+. Our results indicate that under some conditions naive B-cells increase TLR9 expression and proliferate to CpG DNA stimulation without BCR signaling. In addition to its immunological significance, this system should be a valuable method to interrogate the antigenic specificity of naive B-cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S.-O. Yoon, X. Zhang, P. Berner, and Y. S. Choi IL-21 and IL-10 have redundant roles but differential capacities at different stages of plasma cell generation from human germinal center B cells J. Leukoc. Biol., December 1, 2009; 86(6): 1311 - 1318. [Abstract] [Full Text] [PDF] T. M. Garcia-Bates, C. J. Baglole, M. P. Bernard, T. I. Murant, P. J. Simpson-Haidaris, and R. P. Phipps Peroxisome Proliferator-Activated Receptor {gamma} Ligands Enhance Human B Cell Antibody Production and Differentiation J. Immunol., December 1, 2009; 183(11): 6903 - 6912. [Abstract] [Full Text] [PDF] A. D. Henn, J. Rebhahn, M. A. Brown, A. J. Murphy, M. N. Coca, O. Hyrien, T. Pellegrin, T. Mosmann, and M. S. 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