Modelling affinity maturation in the immune system

Abstract

The affinity of antibody for antigen increases during an immune response. This is achieved by mutation of the genes encoding for the antibody and subsequent selection of the best binder. The process takes place in a special microenvironment, the germinal centre. In this dissertation, a mathematical model is presented, which reproduces experimental data on the kinetics of this process and on the affinity maturation observed during the reaction. It further allows predictions to be made about parameters such as the selection rate of centrocytes and the recycling probability of selected centrocytes. Additionally it is shown that termination of somatic hypermutation several days before the end of the germinal centre reaction is beneficial for affinity maturation as is a start of memory cell formation well after the onset of somatic hypermutation. Selection of B cells during the germinal centre reaction is based on antigen recognition and is believed to involve interaction of B cells with membrane bound antigen. It has been shown that such encounter of membrane bound antigen leads to a re-organisation of proteins and lipids such that raft lipids are accumulating in the contact zone. In a second project possible driving forces for such a lipid re-organisation are investigated and the analysis shows that the accumulation of a special lipid sort in the contact zone can be understood by their high affinity for proteins engaged in the contact zone. Interaction between lipids themselves has no positive impact on the accumulation of lipids in the contact zone and strong interactions between lipids may even prohibit the domain formation in the contact zone by the trapping of lipids in patches elsewhere on the cell surface