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. 1992 Dec;11(12):4337–4347. doi: 10.1002/j.1460-2075.1992.tb05533.x

What limits affinity maturation of antibodies in Xenopus--the rate of somatic mutation or the ability to select mutants?

M Wilson 1, E Hsu 1, A Marcuz 1, M Courtet 1, L Du Pasquier 1, C Steinberg 1
PMCID: PMC557007  PMID: 1425571

Abstract

Although the Xenopus immunoglobulin heavy chain locus is structurally and functionally similar to mammalian IgH loci, Xenopus antibodies are limited in heterogeneity, and they mature only slightly in affinity during immune responses. During the antibody response of isogenic frogs to DNP-KLH, mu and upsilon cDNA sequences using elements of the VH1 family were cloned, sequenced and compared with germline counterparts. There were zero to four mutations per sequence, mostly single base substitutions, in the framework and CDRs 1 and 2 of VH. No mutations were found in JH. Since the point mutation rate was only 4- to 7-fold lower than that calculated for mice, affinity maturation does not seem to be limited by mutant availability. Because of a relatively low ratio of replacement to silent mutations in the CDRs and a very high ratio of GC to AT base pairs altered by mutation, it is suggested that the problem results from the absence of an effective mechanism for selecting mutants, which in turn might be related to the absence of germinal centers in Xenopus.

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Selected References

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