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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 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 Citation Map 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. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CpG DNA activation and plasma-cell differentiation of CD27– naive human B cells Jennifer Huggins1, Tina Pellegrin2, Raymond E. Felgar3, Chungwen Wei1, Miguel Brown2, Bo Zheng1, Eric C. B. Milner1, Steven H. Bernstein4, Ignacio Sanz1, and Martin S. Zand2 1 Division of Allergy, Immunology and Rheumatology, 2 Division of Nephrology, 3 Department of Pathology, 4 James P. Wilmot Cancer Center, University of Rochester Medical Center, NY 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– B cells were cultured in a 3-step system: (1) days 0 to 4: CpG, IL-2/10/15; (2) days 4 to 7: IL-2/6/10/15 and anti-CD40L; (3) days 7 to 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. Seventy percent 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 certain conditions, naive B cells increase TLR-9 expression and proliferate to CpG DNA stimulation without BCR signaling. In addition to its immunologic 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: A. Malaspina, S. Moir, A. C. DiPoto, J. Ho, W. Wang, G. Roby, M. A. O'Shea, and A. S. Fauci CpG Oligonucleotides Enhance Proliferative and Effector Responses of B Cells in HIV-Infected Individuals J. Immunol., July 15, 2008; 181(2): 1199 - 1206. [Abstract] [Full Text] [PDF] F. Capolunghi, S. Cascioli, E. Giorda, M. M. Rosado, A. Plebani, C. Auriti, G. Seganti, R. Zuntini, S. Ferrari, M. Cagliuso, et al. CpG Drives Human Transitional B Cells to Terminal Differentiation and Production of Natural Antibodies J. Immunol., January 15, 2008; 180(2): 800 - 808. [Abstract] [Full Text] [PDF] N.-H. Chang, T. McKenzie, G. Bonventi, C. Landolt-Marticorena, P. R. Fortin, D. Gladman, M. Urowitz, and J. E. Wither Expanded Population of Activated Antigen-Engaged Cells within the Naive B Cell Compartment of Patients with Systemic Lupus Erythematosus J. Immunol., January 15, 2008; 180(2): 1276 - 1284. [Abstract] [Full Text] [PDF]

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