Affinity maturation

In immunology, affinity maturation is the process by which B-cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response can elicit antibodies with several logfold greater affinity than in a primary response.

The process is thought to involve two interrelated processes:

1) Somatic hypermutation (SHM): Polymorphisms in the variable, antigen-binding coding sequences (known as complementarity-determining regions) of the immunoglobulin genes clonally accumulate with repeated stimuli, by a process mediated by Activation-Induced (Cytidine) Deaminase. These polymorphisms stochastically alter the binding specifity and binding affinities of the resultant antibodies produced by progeny.

2) Clonal selection: Thought to occur in the germinal centers of the secondary lymphoid organs, B cells that have undergone SHM must compete for limiting growth resources, including the availability of antigen. B cell progeny with the highest affinities for antigen will be selected to survive.  B cell progeny that have undergone SHM, but bind antigen with lower affinity will be outcompeted, and be deleted.  Over several rounds of selection, the resultant secreted antibodies produced will have effectively increased affinities for antigen.