Casting show within the lymph nodes
Computer models and experiments reveal that seemingly random movements of the cells within lymph nodes facilitate optimization of the immune response.
Lymph nodes are the market place for the immune system; cells exchange information regarding invading pathogens here and prepare an appropriate immune response. What appears from the outside to be meaningless and chaotic teeming of millions of cells is actually a flight-path that is highly coordinated and targeted. Researchers from the Helmholtz Centre for Infection Research (HZI) in Braunschweig have recently generated a mathematical model for the movement of immune cells in lymph nodes and were able to use this to explain the results of experiments by international co-operation partners at the Rockefeller University in New York, USA and the New York School of Medicine. Their findings: immune cells go through an optimization cycle during their to-and-fro movements, and at the end of many of these cycle the appropriate immune response to the respectively invading pathogen emerges. These results have been published in a recent issue of the scientific magazine “Cell”.
Ordered chaos within the lymph nodes
So-called germinal centres, within the lymph nodes in which defence cells mature, play a key role during the immune response. They were first described in the 19th century and are spatially divided into a light zone and a dark zone. However, it is nonetheless still not completely understood what happens in these two zones and what role the movements of the immune cells play.
When one typically observes the cells through a microscope, they give the impression that their movements are spontaneous and random. “The apparent chaos in the lymph nodes is actually considerably ordered”, says Michael Meyer-Hermann, Director of the “Systems Immunology” Department. Whether there is a system inherent in the motions of these cells, is a topic that has in the past generated much controversy among scientists. The astounding results from these recent studies however give a clear indication; the exchange of information within the lymph nodes is based on structured movement of the cells, which move back and forth between the two spatially separated zones. During this process, round for round, only those defence cells are selected that are most suited to the respective germ, in order to subsequently make available the optimal weapon to the organism – effective antibodies.
“It is a continuously-repeating cycle of mutations in the dark zone, and a selection of good cells in the light zone”, says Michael Meyer-Hermann. “The immune cells propagate, mutate and slightly change their antibodies in the process. The immune system then evaluates whether these mutations can deliver an improved immune defence – if this is the case, it selects the corresponding cells. Then the cycle begins again. Consequently we have the production of optimized antibodies that are able to efficiently bond with the respective pathogens, thereby marking them for scavenger cells.”
New methods make it possible to track individual cells
In order to be able to examine what pathway individual cells follow through the lymph nodes, American researchers from the New York Rockefeller University and the New York School of Medicine in the USA developed a novel method for representation; the researchers introduced a gene into the genetic information of mice that provides the immune cells with a dye. The unique thing about this particular dye is its capacity to illuminate only when it is activated by a beam of light with a specific wave length. When the researchers want to examine a cell, they activate the dye, causing the cell to illuminate which allows scientists to track it on its pathway through the lymph node.
This highly targeted movement was only able to be disclosed with the aid of the new measuring system together with mathematical modelling of the transitional frequency of occurrence between the zones. “Our analysis of cell movement clearly substantiates the significant role that mathematics plays in biology today”, explains Michael Meyer-Hermann. “In order to solve important scientific problems, predictions are derived from the mathematical models; these predictions then serve as the basis for new experiments, while making data comprehensible.” The new findings regarding selection of immune cells and optimization of an immune response could provide significant help, according to Michael Meyer-Hermann, in the improvement of future vaccinations for which the formation of effective antibodies within the human body plays an important role.
Original article: Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter. Gabriel D. Victora, Tanja A. Schwickert, David R. Fooksman, Alice O. Kamphorst, Michael Meyer-Hermann, Michael L. Dustin and Michel C. Nussenzweig. Cell, Volume 143, Issue 4, 592-605, 12 November 2010. doi:10.1016/j.cell.2010.10.032