The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20081160
The Journal of Experimental Medicine, Vol. 205, No. 13, 3019-3029
The Rockefeller University Press, 0022-1007 $30.00
© Figge et al.
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ARTICLE

 Deriving a germinal center lymphocyte migration model from two-photon data

Marc Thilo Figge1, Alexandre Garin2, Matthias Gunzer3, Marie Kosco-Vilbois2, Kai-Michael Toellner4, and Michael Meyer-Hermann1

1 Frankfurt Institute for Advanced Studies, D-60438 Frankfurt am Main, Germany
2 NovImmune SA, CH-1228 Plan-les-Ouates, Switzerland
3 Institute for Molecular and Clinical Immunology, Otto-von-Guericke-University, D-39120 Magdeburg, Germany
4 Medical Research Council Centre for Immune Regulation, The University of Birmingham, Edgbaston, B15 2TT Birmingham, England, UK

CORRESPONDENCE Marc Thilo Figge: figge{at}fias.uni-frankfurt.de OR Michael Meyer-Hermann: m.meyer-hermann{at}fias.uni-frankfurt.de

Recently, two-photon imaging has allowed intravital tracking of lymphocyte migration and cellular interactions during germinal center (GC) reactions. The implications of two-photon measurements obtained by several investigators are currently the subject of controversy. With the help of two mathematical approaches, we reanalyze these data. It is shown that the measured lymphocyte migration frequency between the dark and the light zone is quantitatively explained by persistent random walk of lymphocytes. The cell motility data imply a fast intermixture of cells within the whole GC in approximately 3 h, and this does not allow for maintenance of dark and light zones. The model predicts that chemotaxis is active in GCs to maintain GC zoning and demonstrates that chemotaxis is consistent with two-photon lymphocyte motility data. However, the model also predicts that the chemokine sensitivity is quickly down-regulated. On the basis of these findings, we formulate a novel GC lymphocyte migration model and propose its verification by new two-photon experiments that combine the measurement of B cell migration with that of specific chemokine receptor expression levels. In addition, we discuss some statistical limitations for the interpretation of two-photon cell motility measurements in general.

Abbreviations used: FDC, follicular DC; GC, germinal center.

© 2008 Figge et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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