Peter Parham

“Somatic hypermutation gives rise to B cells bearing mutant immunoglobulin molecules on their surface. Some of these mutant immunoglobulins have substitutions in the antigen-binding site that increase its affinity for the antigen. B cells bearing these mutant high-affinity immunoglobulin receptors compete most effectively for binding to antigen and are preferentially selected to mature into antibody-secreting plasma cells. The mutant antibodies that emerge from the selection do not have a random distribution of amino-acid substitutions. The changes are concentrated at positions in the heavy-chain and light-chain CDR loops that form the antigen-binding site and directly contact antigen. As the adaptive immune response to infection proceeds, antibodies of progressively higher affinity for the infecting pathogen are produced – a phenomenon called affinity maturation. Affinity maturation is a process of evolution in which variant immunoglobulins generated in a random manner are subjected to selection for improved binding to a pathogen. It achieves in a few days what would require thousands, if not millions, of years of classical Darwinian evolution in a conventional gene. This capacity for extraordinarily rapid evolution in pathogen-binding immunoglobulins is a major factor in allowing the human immune system to keep up with the generally faster-evolving pathogens.”