The Lymph Node B Cell Immune Response: Dynamic Analysis In-Silico

Lymph nodes are organs in which lymphocytes respond to antigens to generate, among other cell types, plasma cells that secrete specific antibodies and memory lymphocytes for enhanced future responses to the antigen. To achieve these ends, the lymph node (LN) has to orchestrate the meeting and interactions between the antigen and various cell types including the rare clones of B cells and T cells bearing receptors for the antigen. The process is dynamic in essence and involves chemotaxis of responding cells through various anatomical compartments of the LN and selective cell differentiation, proliferation and programmed death. Understanding the LN requires a dynamic integration of the mass of data generated by extensive experimentation. Here, we present a fully executable, bottom-up computerized model of the LN using the visual language of Statecharts and the technology of reactive animation (RA) to create a dynamic front-end. We studied the effects of amount of antigen and LN size on the emergent properties of lymphocyte dynamics, differentiation and anatomic localization. The dynamic organization of the LN visualized by RA sheds new light on how the immune system transforms antigen stimulation into a highly sensitive, yet buffered response.