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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4088-4096. Prepublished online as a Blood First Edition Paper on August 26, 2004; DOI 10.1182/blood-2003-12-4291. This Article Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2003-12-4291v1 104/13/4088    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 Basso, K. Articles by Dalla-Favera, R. Search for Related Content PubMed PubMed Citation Articles by Basso, K. Articles by Dalla-Favera, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 6, 2004 Accepted August 2, 2004 Tracking CD40 signaling during germinal center development Katia Basso, Ulf Klein, Huifeng Niu, Gustavo A Stolovitzky, Yuhai Tu, Andrea Califano, Giorgio Cattoretti, and Riccardo Dalla-Favera* Institute for Cancer Genetics, Columbia University, New York, NY, USA IBM T.J. Watson Research Center, Yorktown Heights, NY, USA Institute for Cancer Genetics, Columbia University, New York, NY, USA; Joint Centers for Systems Biology, Columbia University, New York, NY, USA Institute for Cancer Genetics, Columbia University, New York, NY, USA; Department of Pathology and Genetics & Development, Columbia University, New York, NY, USA * Corresponding author; email: rd10{at}columbia.edu. Substantial evidence indicates that signaling through the CD40 receptor (CD40) is required for germinal center (GC) and memory B-cell formation. However, it is not fully understood at which stages of B-cell development the CD40 pathway is activated in vivo. To address this question, we induced CD40 signaling in human transformed GC B-cells in vitro and identified a CD40 gene expression signature by DNA microarray analysis. This signature was then investigated in the gene expression profiles of normal B-cells and found in pre- and post-GC B-cells (naive and memory) but, surprisingly, not in GC B-cells. This finding was validated in lymphoid tissues by showing that the NF-B transcription factors, which translocate to the nucleus upon CD40 stimulation, are retained in the cytoplasm in most GC B-cells, indicating the absence of CD40 signaling. Nevertheless, a subset of centrocytes and B-cells in the subepithelium showed nuclear staining of multiple NF-B subunits suggesting that a fraction of naive and memory B-cells may be subject to CD40 signaling or to other signals that activate NF-B. Together, these results show that GC expansion occurs in the absence of CD40 signaling, which, instead, may act only in the initial and final stages of the GC reaction. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Kaku and T. L. Rothstein Fas Apoptosis Inhibitory Molecule Enhances CD40 Signaling in B Cells and Augments the Plasma Cell Compartment J. Immunol., August 1, 2009; 183(3): 1667 - 1674. [Abstract] [Full Text] [PDF] M. Saito, U. Novak, E. Piovan, K. Basso, P. Sumazin, C. Schneider, M. Crespo, Q. Shen, G. Bhagat, A. Califano, et al. BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma PNAS, July 7, 2009; 106(27): 11294 - 11299. [Abstract] [Full Text] [PDF] W. Ci, J. M. Polo, L. Cerchietti, R. Shaknovich, L. Wang, S. N. Yang, K. Ye, P. Farinha, D. E. Horsman, R. D. Gascoyne, et al. 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