Valency or wählency: Is the epitope diversity of the B‐cell response regulated or chemically determined?

Abstract

Summary 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.

Beyond binding: antibody effector functions in infectious diseases

“…2). Consequently, innate immune activation only occurs upon antibody–antigen multimerization and complex formation, which enhances the avidity of the inter actions of FcRs or CLRs on the cell surface with antibody Fc domains 73,74 . This ensures that innate immune effector function is only deployed in the presence of the pathogen (which is bound by several antibodies simultaneously) and enables innate immune cells to integrate information across multiple and sometimes heterogeneous FcRs or CLRs that aggregate on the surface of effector cells.…”

Removal of B cell epitopes as a practical approach for reducing the immunogenicity of foreign protein-based therapeutics☆

“…As we have discussed above, peptide-scanning techniques are not useful, because they usually fail to detect conformational epitopes. Polyclonal antibodies cannot be used for epitope analysis, because there is a limitation of the number of antibody molecules that can bind to the antigen at one time and epitopes can be silent in the presence of a large amount of antibodies to other epitopes until the main epitopes are eliminated by mutation [85, 86]. The best solution is the production of a panel of monoclonal antibodies so that the binding of each can be analyzed and studied [87].…”

The Biological Activity of Serum IgE Changes over the Course of a Primary Response

“…Consequently, changes in the number of epitopes recognized in vivo could potentially have modulating effects on mast‐cell function. Changes in epitope patterns have been proposed to account for differences between RAST and skin‐test results [6], and have been argued to influence the ability of IgG to activate effector mechanisms [46]. Although the present study was unable to address this question, there is some evidence that the number of epitopes to which the immune system responds can change during the course of a response [47, 48].…”