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International Immunology Advance Access originally published online on March 11, 2008
International Immunology 2008 20(4):615-623; doi:10.1093/intimm/dxn020
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Mechanisms of organogenesis of primary lymphoid follicles

Tilo Beyer1,2 and Michael Meyer-Hermann2

1 Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University, Leipziger Strasse 44, 39120 Magdeburg, Germany
2 Frankfurt Institute for Advanced Studies, Johann Wolfgang Goethe-University, Ruth-Moufang-Strasse 1, 60438 Frankfurt am Main, Germany

Correspondence to: T. Beyer; E-mail: tilo.beyer{at}med.ovgu.de

Primary lymphoid follicles (PLFs) in secondary lymphoid tissue (SLT) of mammals are the backbone for the formation of follicular dendritic cell (FDC) networks. These are important for germinal center reactions during which affinity maturation creates optimized antibodies in adaptive immune responses. In the context of organogenesis, molecular requirements for the formation of follicles have been identified. The present study complements these findings with a simulation of the dynamics of the PLF formation, and a critical analysis of the relevant molecular interactions. In contrast to other problems of pattern formation, the homeostasis of cell populations in SLTs is not governed by a growth-death balance but by a flow equilibrium of migrating cells. The influx of cells into these tissues has been extensively studied. However, less information is available about the efflux of lymphocytes from SLTs. This study formulates the minimal requirements for cell efflux that guarantee a flow equilibrium and, thus, a stable PLF. The model predicts that in addition to already identified regulatory mechanisms, a negative regulation of the generation of FDCs is required. Furthermore, a comparison with data concerning the microanatomy of SLTs yields the conclusion that dynamical changes of the lymphatic endothelium during the formation of FDC networks are necessary to understand the genesis and maintenance of follicles.

Keywords: chemotaxis, follicular dendritic cells, lymphocytes, negative regulation, spleen, lymph nodes

Transmitting editor: T. Watanabe

Received 4 September 2007, accepted 5 February 2008.


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