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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2381-2389. Prepublished online as a Blood First Edition Paper on July 9, 2007; DOI 10.1182/blood-2007-02-075143. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-02-075143v1 110/7/2381    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 Guo, F. Articles by Weih, F. Search for Related Content PubMed PubMed Citation Articles by Guo, F. Articles by Weih, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 16, 2007 Accepted July 2, 2007 Constitutive alternative NF-B signaling promotes marginal zone B cell development but disrupts the marginal sinus and induces HEV-like structures in the spleen Feng Guo, Debra Weih, Elke Meier, and Falk Weih* Department of Immunology, Leibniz-Institute for Age Research - Fritz-Lipmann-Institute, Jena, Germany Friedrich-Schiller-University, Jena, Germany * Corresponding author; email: fweih{at}fli-leibniz.de. Nuclear factor (NF)-B plays a crucial role in B cell and lymphoid organ development. Here, we studied the consequences of constitutive, signal-independent activation of the alternative NF-B pathway for the splenic marginal zone (MZ). In contrast to nfkb2-/- mice, which lack both p100 and p52, mice that lack only the inhibitory p100 precursor but still express the p52 subunit of NF-B2 (p100-/-) had markedly elevated MZ B cell numbers. Both cell intrinsic mechanisms and increased stromal expression of vascular cell adhesion molecule-1 (VCAM-1) contributed to the accumulation of MZ B cells in p100-/- spleen. While migration of p100-/- MZ B cells towards the lysophospholipid sphingosine-1 phosphate (S1P) was not affected, CXCL13-stimulated chemotaxis was impaired, correlating with reduced migration of MZ B cells into follicles in response to LPS. Strikingly, p100 deficiency resulted in the absence of a normal marginal sinus, strongly induced expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and glycosylated cell adhesion molecule-1 (GlyCAM-1), and the formation of non-functional ectopic high endothelial venule (HEV)-like structures in the red pulp. Thus, constitutive activation of the alternative NF-B pathway favors MZ B cell development and accumulation but leads to a disorganized spleen microarchitecture. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. J. Bende, F. van Maldegem, and C. J.M. van Noesel Chronic inflammatory disease, lymphoid tissue neogenesis and extranodal marginal zone B-cell lymphomas Haematologica, August 1, 2009; 94(8): 1109 - 1123. [Abstract] [Full Text] [PDF] E. T. Cadman, A. Y. Abdallah, C. Voisine, A.-M. Sponaas, P. Corran, T. Lamb, D. Brown, F. Ndungu, and J. Langhorne Alterations of Splenic Architecture in Malaria Are Induced Independently of Toll-Like Receptors 2, 4, and 9 or MyD88 and May Affect Antibody Affinity Infect. Immun., September 1, 2008; 76(9): 3924 - 3931. [Abstract] [Full Text] [PDF] F. Guo, S. Tanzer, M. Busslinger, and F. Weih Lack of nuclear factor-{kappa}B2/p100 causes a RelB-dependent block in early B lymphopoiesis Blood, August 1, 2008; 112(3): 551 - 559. [Abstract] [Full Text] [PDF]

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