Valency or wählency: is the epitope diversity of the B-cell response regulated or chemically determined?

For almost a century, the humoral immune response has been monitored principally by the measurement of antibody concentrations, although antibody affinity and isotype have also long been acknowledged as critical to their biological activity. In this report, it is argued that these measures alone may provide a poor measure of the activity of serum antibodies. A B-cell response that is directed against multiple epitopes on a protein can form immune complexes bearing multiple antibody molecules. This is essential for the efficient initiation of processes such as the complement cascade and the activation of leucocytes via Fc receptors. These processes can be dramatically enhanced when B cells target a greater number of epitopes on any antigen. Evidence that the epitope diversity of an immune response may vary between individuals, and that it may vary in an individual over time, is reviewed. This variability is likely to be influenced by a number of host-specific factors in addition to antigen chemistry. The appropriateness of the chemically deterministic term 'antigen valency' to describe the number of epitopes recognized by an individual's B-cell response is discussed, and the term 'wählency' to emphasize the situational nature of B-cell epitopes is introduced.