Lecture - Optimisation of adaptive antibody responses

Upon infection innate immune responses are mounted which control but do not clear the infection. Adaptive immune responses by T cells and by antibody forming cells are mounted much slower but are pre-selected to optimally fight the infection. Specialised antibodies are essential not only for final clearance of infections but also for vaccination. At every vaccination, a so-called germinal centre (GC) reaction is initiated. In a GC, B lymphocytes divide and mutate their encoded antibody. The mutated B cell is subsequently subject to selection giving rise to an evolutionary process of generating optimised antibodies and memory within the organism on a time scale of 10 days. The functional principles of how B cells get diversified and selected will be presented. A particular emphasis is set on the mutual interaction of mathematical models and multi-photon imaging. These two powerful techniques together were able to unravel the limiting role of T cell help in the GC for B cell selection. It will be explained, why T cells control the number of divisions of B cells. More recently, the analysis of brainbow experiments allowed to monitor different clones in their evolution within the GC. This analysis revealed bursts of clones which may dominate a whole GC reaction as well as co-existence of many clones on long term. These findings have major implications for the design and development of new vaccines.

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