Abstract
In a pair of articles, we present a generalized quantitative model for the homeostatic function of clonal humoral immune system. In this second paper, we describe how antibody production controls 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. 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 diverse targets and shared recognition of particular antigens by multiple antibody clones contribute to the maintenance of antigen control. We also argue that natural antibodies are none else than the result of thymus-independent responses against immunological self. We interpret and explain antibody production and function in a virtual molecular interaction space and as a network of interactions. Indeed, the general quantitative (GQM) 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 the sequence and interaction database data.
Highlights
Assuming that antibodies are produced with the intent of regulating antigen availability, best control over antigen concentration is achieved when the concentration of antibody is close to the KD (Fig.1)
The situation drastically changes if we look at local concentrations instead of plasma concentration, where even a single antibody secreting effector cells (ASC) can generate adequate amounts of antibody
We have introduced homeostatic antibody model based on the assumption that the clonal humoral immune system seeks after an equilibrium between antibody and antigen
Summary
By definition antigens are molecules recognized by antibodies. Most definitions fail to further elaborate what exactly is meant by recognition. Assuming that antibodies are produced with the intent of regulating antigen availability, best control over antigen concentration is achieved when the concentration of antibody is close to the KD (Fig.1) In our map this zone for a range of [Ab] and KD values is defined by a line where [Ab] = KD, which is the line representing 50% saturation of the antigen (Fig 1). The range of KD values includes affinity constants usually observed 1 for antibody‐ antigen interactions (of KD=10‐6–10‐10 M) but extends to both lower and higher values to provide flexibility for interpreting apparent affinities. Please note that these are exactly the same dimensions, which we use in our accompanying sister paper on B‐cell development (Prechl, submitted). We will consider a single fluidic compartment, the blood plasma for this theoretical framework, with proper adjustments the model can be possibly extended to include the extracellular space and mucosal surfaces – sites of key importance for immunological action
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