Deriving a germinal center lymphocyte migration model from two-photon data
Open Access
- 1 December 2008
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 205 (13), 3019-3029
- https://doi.org/10.1084/jem.20081160
Abstract
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.Keywords
This publication has 57 references indexed in Scilit:
- Germinal-Center Organization and Cellular DynamicsImmunity, 2007
- In vivo imaging studies shed light on germinal-centre developmentNature Reviews Immunology, 2007
- Lymph node topology dictates T cell migration behaviorThe Journal of Experimental Medicine, 2007
- In vivo imaging of germinal centres reveals a dynamic open structureNature, 2007
- Tracking germinal center B cells expressing germ-line immunoglobulin γ1 transcripts by conditional gene targetingProceedings of the National Academy of Sciences, 2006
- A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivoBlood, 2004
- Balanced responsiveness to chemoattractants from adjacent zones determines B-cell positionNature, 2002
- Recycling Probability and Dynamical Properties of Germinal Center ReactionsJournal of Theoretical Biology, 2001
- Cyclic re-entry of germinal center B cells and the efficiency of affinity maturationImmunology Today, 1993
- Theoretical studies of clonal selection: Minimal antibody repertoire size and reliability of self-non-self discriminationJournal of Theoretical Biology, 1979