Affinity maturation
In
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 fold greater affinity than in a primary response. Affinity maturation primarily occurs on membrane immunoglobulin of germinal center B cells and as a direct result of somatic hypermutation (SHM) and selection by TFH cells.[1]
In vivo
The process is thought to involve two interrelated processes, occurring in the germinal centers of the secondary lymphoid organs:
- germinal centers present antigen to the B cells, and the B cell progeny with the highest affinities for antigen, having gained a competitive advantage, are favored for positive selection leading to their survival. Positive selection is based on steady cross-talk between TFH cells and their cognate antigen presenting GC B cell. Because a limited number of TFH cells reside in the germinal center, only highly competitive B cells stably conjugate with TFH cells and thus receive T cell-dependent survival signals. 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.[3]
In vitro
Like the natural prototype, the in vitro affinity maturation is based on the principles of mutation and selection. The in vitro affinity maturation has successfully been used to optimize antibodies, antibody fragments or other
error-prone PCR. In addition, the genetic diversity can be increased by chain shuffling. Two or three rounds of mutation and selection using display methods like phage display usually results in antibody fragments with affinities in the low nanomolar range.[3]
References
- S2CID 20168324.
- PMID 17576170.
- ^ ISBN 978-3-527-31453-9.