Molecular economy and antibody function: the evolution of a Protecton

The humoral immune response protects against a very large array of pathogens which attempt to escape immune recognition by changing the antigens they display. When looked at from the point of two competing sets of DNA (i.e., the pathogens vs. the host), there is a vastly larger pool of mutating pathogen DNA than in, say, a mouse. The stratagems that allow a tiny fraction of the mouse's genome to effectively compete with a hugely diverse array of pathogens is analyzed in terms of how antibody functions and how the immune system avoids such pitfalls as self-recognition and destruction. This review is a more general description of a lengthy series of papers which detailed the evolution of the Protecton. Starting from the obvious, that is the concentration-dependence of antibody function, it is apparent that the functional antibody repertoire must be relatively small if a sufficient concentration of specific antibody is to be produced in time to arrest the growth of pathogens and eventually eliminate them. Thus, commonly quoted estimates of antibody repertoires in the range from greater than 10(10) to "complete" (infinite?) must be seriously in error. Other well known "facts", such as D-diversity, and B cell signaling by receptor aggregation are also shown to be lacking in biological commonsense.