|
|
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.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
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
From the Institute for Cancer Genetics, the Department of Pathology and Genetics and Development, and the Joint Centers for Systems Biology, Columbia University, New York, NY; and IBM T. J. Watson Research Center, Yorktown Heights, NY.
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 nuclear factor- B (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 may act only in the initial and final stages of the GC reaction. (Blood. 2004;104: 4088-4096)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
G Kapatai and P Murray
Contribution of the Epstein Barr virus to the molecular pathogenesis of Hodgkin lymphoma
J. Clin. Pathol.,
December 1, 2007;
60(12):
1342 - 1349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Stewart, W. Wei, A. Challa, R. J. Armitage, J. R. Arrand, M. Rowe, L. S. Young, A. Eliopoulos, and J. Gordon
CD154 Tone Sets the Signaling Pathways and Transcriptome Generated in Model CD40-Pluricompetent L3055 Burkitt's Lymphoma Cells
J. Immunol.,
September 1, 2007;
179(5):
2705 - 2712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Cattoretti, R. Shaknovich, P. M. Smith, H.-M. Jack, V. V. Murty, and B. Alobeid
Stages of Germinal Center Transit Are Defined by B Cell Transcription Factor Coexpression and Relative Abundance
J. Immunol.,
November 15, 2006;
177(10):
6930 - 6939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Cattoretti, M. Buttner, R. Shaknovich, E. Kremmer, B. Alobeid, and G. Niedobitek
Nuclear and cytoplasmic AID in extrafollicular and germinal center B cells
Blood,
May 15, 2006;
107(10):
3967 - 3975.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Ruiz-Ballesteros, M. Mollejo, A. Rodriguez, F. I. Camacho, P. Algara, N. Martinez, M. Pollan, A. Sanchez-Aguilera, J. Menarguez, E. Campo, et al.
Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis
Blood,
September 1, 2005;
106(5):
1831 - 1838.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Feuerhake, J. L. Kutok, S. Monti, W. Chen, A. S. LaCasce, G. Cattoretti, P. Kurtin, G. S. Pinkus, L. de Leval, N. L. Harris, et al.
NF{kappa}B activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes
Blood,
August 15, 2005;
106(4):
1392 - 1399.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
