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PMID: 1425571 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 11 ·No. 12 ·1992-12-00 ·Pages 4337-47

Wilson M, Hsu E, Marcuz A, Courtet M, Du Pasquier L, Steinberg C

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.

Related Genes
IgH
MeSH Terms
Amino Acid Sequence Animals Antibody Formation/genetics Base Sequence DNA DNA Mutational Analysis Hemocyanins/immunology Immunoglobulin Heavy Chains/genetics Molecular Sequence Data Mutation Polymerase Chain Reaction Xenopus laevis
Chemicals
Immunoglobulin Heavy Chains DNA Hemocyanins keyhole-limpet hemocyanin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wilson M
Basel Institute for Immunology, Switzerland.
Hsu E
Marcuz A
Courtet M
Du Pasquier L
Steinberg C
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54 references, click to expand
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-12-00
Pages
4337-47
Language
English
Region
England
NLM ID
8208664
PMCID
PMC557007
Subset
IM
Databases
GENBANK
M94778, M94780, M94785, M94787, M94788, M94789, M94790, M94791, M94796, M94797, M94801, M94804, M94805, M94806, M94807, M94812, M94818, M94821, M94822, M94823, M94825, M94826, M94828, M94832, M94835, M94836, M94838, M94841, M94850, M94854
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