Somatic hypermutation of immunoglobulin genes in human neonates

The antibody response in the young infant is limited in several ways; in particular, responses generally are of low affinity and restricted to IgM. This raises the question whether the affinity maturation process, consisting of somatic mutation of immunoglobulin genes coupled with selection of high‐...

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Bibliographic Details
Published in:Clinical and experimental immunology 1997-05, Vol.108 (2), p.366-374
Main Authors: RIDINGS, J., NICHOLSON, I. C., GOLDSWORTHY, W., HASLAM, R., ROBERTON, D. M., ZOLA, H.
Format: Article
Language:English
Subjects:
affinity maturation
Amino Acid Sequence
Base Sequence
Biological and medical sciences
Cloning, Molecular
Fetal Blood
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genes, Immunoglobulin - genetics
Genes, Immunoglobulin - immunology
Genetics of the immune response
Humans
Immunobiology
immunoglobulin genes
immunoglobulin somatic mutation
Immunoglobulin Variable Region - genetics
Infant
Infant, Newborn - immunology
Molecular Sequence Data
Mutation - immunology
neonatal antibody response
Nucleic Acid Heteroduplexes - immunology
Original
Sequence Analysis, DNA
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Summary:The antibody response in the young infant is limited in several ways; in particular, responses generally are of low affinity and restricted to IgM. This raises the question whether the affinity maturation process, consisting of somatic mutation of immunoglobulin genes coupled with selection of high‐affinity variants, is operative in the neonate. Re‐arranged VH6 genes were amplified by polymerase chain reaction (PCR) from cord blood and from peripheral blood of infants. Heteroduplex analysis detected mutation in only 2/18 cord blood samples, while mutations were seen from about 10 days of age onwards. Cloning and sequencing of mutated neonatal VH6 genes showed that mutated sequences contained relatively few mutations (one to three mutations per sequence) compared with published values of about 10 in adult IgM sequences. Selection was not evident in the majority of neonatal samples. Thus mutation can occur in the human neonate, but is minimal and generally not accompanied by selection. The age at which affinity maturation develops effectively is yet to be defined.
ISSN:0009-9104
1365-2249
DOI:10.1046/j.1365-2249.1997.3631264.x