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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
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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
92:(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 SHM is still not known, a major role for the
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has been discussed. The increased mutation rate results in 1-2 mutations per CDR and, hence, per cell generation. The mutations alter the binding specificity and binding affinities of the resultant antibodies.
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can elicit antibodies with several fold greater affinity than in a primary response. Affinity maturation primarily occurs on membrane immunoglobulin of
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102:: B cells that have undergone SHM must compete for limiting growth resources, including the availability of antigen and paracrine signals from
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during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater
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The process is thought to involve two interrelated processes, occurring in the germinal centers of the secondary lymphoid organs:
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affinity maturation has successfully been used to optimize antibodies, antibody fragments or other
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cells reside in the germinal center, only highly competitive B cells stably conjugate with T
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cells and their cognate antigen presenting GC B cell. Because a limited number of T
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usually results in antibody fragments with affinities in the low nanomolar range.
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Roskos L.; Klakamp S.; Liang M.; Arends R.; Green L. (2007). Stefan Dübel (ed.).
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affinity maturation is based on the principles of mutation and selection. The
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Teng, G.; Papavasiliou, F.N. (2007). "Immunoglobulin
Somatic Hypermutation".
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175:. Two or three rounds of mutation and selection using display methods like
88:: Mutations in the variable, antigen-binding coding sequences (known as
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Victora, Gabriel D.; Nussenzweig, Michel C. (2012-04-23).
171:. In addition, the genetic diversity can be increased by
159:. Random mutations inside the CDRs are introduced using
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295:. Weinheim: Wiley-VCH. pp. 145–169.
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94:activation-induced (cytidine) deaminase
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265:10.1146/annurev.genet.41.110306.130340
214:10.1146/annurev-immunol-020711-075032
90:complementarity-determining regions
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293:Handbook of Therapeutic Antibodies
59:B cells and as a direct result of
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143:Like the natural prototype, the
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43:with increased affinity for
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202:Annual Review of Immunology
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16:Cellular process in B cells
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112:follicular dendritic cells
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27:is the process by which
63:(SHM) and selection by
86:Somatic hypermutation
61:somatic hypermutation
25:affinity maturation
198:"Germinal Centers"
53:secondary response
302:978-3-527-31453-9
157:antibody mimetics
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100:Clonal selection
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163:, chemical
35:-activated
323:Immunology
183:References
49:affinities
41:antibodies
21:immunology
222:0732-0582
161:radiation
317:Category
273:17576170
238:20168324
230:22224772
165:mutagens
149:in vitro
145:in vitro
138:In vitro
132:antigen.
39:produce
153:peptide
76:In vivo
45:antigen
37:B cells
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110:. The
234:S2CID
108:cells
69:cells
51:. A
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226:PMID
218:ISSN
33:cell
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167:or
19:In
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129:FH
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