Searching for the optimal antibody
A model describes how antibodies of optimal quality and quantity are generated
B-cells play a crucial role in the defence against pathogens. They are in charge of the production of antibodies and are the only cells in the body which actively mutate their DNA in order to invent new antibodies. This allows them not only to detect intruders, but also to render pathogens harmless by means of weapons that are tailor-made for any threat that may be encountered. The successful production of optimal antibodies in sufficient number and of sufficient effectiveness is subject to a number of mechanisms. Scientists of the Helmholtz Centre for Infection Research (HZI) in Braunschweig used a mathematical model to identify the, thus far, first and only mechanism that enhances both the quantity and the effectiveness of the antibodies, which has been published in "The Journal of Immunology".
New antibodies are produced by B-cells in the lymph nodes of the body. Before this takes place, these B-cells undergo a selection process in certain regions of the lymph nodes, called germinal centres. The immune cells proliferate and mutate which causes changes in the antibodies they produce. In an ideal scenario, the optimisation cycle of mutation and selection ultimately results in antibodies that can optimally bind to certain structures of pathogens, so-called antigens, and neutralise them effectively. "The B-cells undergo an evolutionary process to keep improving," says Prof Michael Meyer-Hermann, head of the "System Immunology" department at the HZI.
During the selection process, the B-cells undergo a number of selection procedures. Each of these procedures can be intensified or attenuated. "The effect is quite intuitive to understand: If you increase the selection pressure, you get fewer antibodies, but these are of very good quality. You get the reverse if you reduce the selection pressure: more antibodies, but of poorer quality," says Meyer-Hermann. To produce quantity and quality in the same step is the ideal evolutionary scenario. Until recently, it was believed that the ideal case was not possible.
However, Meyer-Hermann used a mathematical model to simulate the various evolutionary processes, which B-cells undergo in the course of antibody production. The scientists aimed to find out how much of a positive effect the individual steps have on the selection process. "We managed to show that one of the three regulatory principles we investigated has just a positive effect," says Meyer-Hermann.
In the next step, immunologists need to do experiments to identify and understand the underlying mechanism. "If this is successful, it would be feasible to control the production of antibodies with individually adapted medications and to then support or suppress the efficiency of the body's inherent immune defence to fit the medical context," says Meyer-Hermann. This work is a contribution to the BMBF-sponsored eMED project, SYSIMIT, which investigates the early detection and prevention of graft rejection. Since the insights gained may ultimately lead to the development of individualised therapies, Meyer-Hermann's research is also sponsored by the Helmholtz Association's iMed initiative for personalised medicine.
Michael Meyer-Hermann, Overcoming the Dichotomy of Quantity and Quality in Antibody Responses.
The Journal of Immunology; 2014, DOI:10.4049/jimmunol.1401828
The "Systems Immunology" department of the HZI investigates the mathematical modelling of immunological processes. The department is associated with the Braunschweig Integrated Centre for Systems Biology (BRICS), a new research centre for Systems Biology that has been established jointly by the HZI and the Technical University Braunschweig.