TY - JOUR T1 - A generalized quantitative antibody homeostasis model: antigen saturation, natural antibodies and a quantitative antibody network JF - bioRxiv DO - 10.1101/065748 SP - 065748 AU - József Prechl Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/07/26/065748.abstract N2 - In a pair of articles we present a generalized model for the homeostatic function of clonal humoral immune system. Our model assumes that the essence of antibody homeostasis is to maintain a balance between the saturation of B-cell receptors (BCR) by antigen and the saturation of antigen by antibodies. In this paper we describe how antibody production results in the saturation of antigens and the network of antibody interactions that emerges in the epitome space with the establishment of the immune system.Efficient control of antigens, be it self or foreign, requires the maintenance of antibody concentrations that saturate antigen to relevant levels. This in turn means that depending on the affinity of the interaction high or low free antibody concentrations should be maintained for low and high affinity antibodies, respectively. Simple calculations suggest that the observed diverse recognition of antigens by natural antibodies is only possible by cross-reactivity whereby particular clones of antibodies bind to different targets and contribute to the maintenance of free antibody concentration. This shared recognition is a key feature of natural antibodies. Furthermore, we argue that natural antibodies are none else than the result of thymus independent responses against immunological self. The role of the humoral immune system is the homeostatic control of this compartment, controlling molecular crowding and catabolism and protecting barriers of the compartment and beyond. We also interpret and explain antibody production and function in a virtual molecular interaction space and as a network of interactions. Indeed the model we propose is in agreement with earlier models, confirms some assumptions and presumably provides the theoretical basis for the construction of a real antibody network using sequence and database data. ER -