Germinal centre B-lymphocytes have been identified in malignant follicular lymphoma. It is therefore believed that a malignancy in germinal centre reactions may even induce the development of follicular lymphoma. The relevant mechanism in germinal centres is not known and open for speculation. However, characteristic morphologies of malignant germinal centres have been observed. The aim of this project is to contribute to this discussion from a theoretical point of view. Theories for the germinal centre reaction have already been developed, especially by the authors of this proposal. Michael Meyer-Hermann developed the first theory attempting to describe and explain the specific morphology of germinal centres and its time course. Individual-based models provide a suitable basis in order to understand how possible malfunctions of the germinal centre reaction are reflected in the morphology of the resulting malignant germinal centre. The results can be compared to observed malignant germinalcentres. A fundamental requirement for this objective is a detailed description of molecular mechanisms involved in the germinal centre reaction. In the individual-based models using local cell interactions those processes have been included only effectively (signal transmission and chemo taxis). The expertise of the Centre for Mathematical Biology (CMB),part of the Mathematical Institute at Oxford University, in reaction-diffusion systems provides the experience necessary to realize an explicit and numerically feasible inclusion of molecular processes into the simulation. In addition spending time at the CMB will enable Michael Meyer-Hermann to establish collaboration to leading experimental institutions in the field of germinal centres (situated in Birmingham and Cambridge). Thus, the theory can be closely linked to current experimental knowledge. Finally, the CMB is developing expertise in simulation of tumour growth.
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