In Vivo Affinity Maturation
The process is thought to involve two interrelated processes, occurring in the germinal centers of the secondary lymphoid organs:
- Somatic hypermutation (SHM): Mutations in the variable, antigen-binding coding sequences (known as complementarity-determining regions (CDR)) of the immunoglobulin genes. The mutation rate is up to 1,000,000 times higher than in cell lines outside the lymphoid system. Although the exact mechanism of the somatic hypermutation is still not known, a major role for the Activation-Induced (Cytidine) Deaminase has been discussed. The increased mutation rate result in 1-2 mutations per CDR and cell generation. The mutations alter the binding specificity and binding affinities of the resultant antibodies.
- Clonal selection: B cells that have undergone SHM must compete for limiting growth resources, including the availability of antigen. The follicular dendritic cells (FDCs) of the germinal centers present antigen to the B cells, and only the 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 out-competed, and be deleted. Over several rounds of selection, the resultant secreted antibodies produced will have effectively increased affinities for antigen.
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