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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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| Published in: | Clinical and experimental immunology 1997-05, Vol.108 (2), p.366-374 |
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| Main Authors: | , , , , , |
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| container_end_page | 374 |
| container_issue | 2 |
| container_start_page | 366 |
| container_title | Clinical and experimental immunology |
| container_volume | 108 |
| creator | RIDINGS, J. NICHOLSON, I. C. GOLDSWORTHY, W. HASLAM, R. ROBERTON, D. M. ZOLA, H. |
| description | 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. |
| doi_str_mv | 10.1046/j.1365-2249.1997.3631264.x |
| format | article |
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C. ; GOLDSWORTHY, W. ; HASLAM, R. ; ROBERTON, D. M. ; ZOLA, H.</creator><creatorcontrib>RIDINGS, J. ; NICHOLSON, I. C. ; GOLDSWORTHY, W. ; HASLAM, R. ; ROBERTON, D. M. ; ZOLA, H.</creatorcontrib><description>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.</description><identifier>ISSN: 0009-9104</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1046/j.1365-2249.1997.3631264.x</identifier><identifier>PMID: 9158112</identifier><identifier>CODEN: CEXIAL</identifier><language>eng</language><publisher>Oxford BSL: Blackwell Science Ltd</publisher><subject>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</subject><ispartof>Clinical and experimental immunology, 1997-05, Vol.108 (2), p.366-374</ispartof><rights>Blackwell Science Ltd, Oxford</rights><rights>1997 INIST-CNRS</rights><rights>1997 Blackwell Science Ltd 1997</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6023-a563f3e54e11aead42055cb76cbdc5becbb95068f2ca799dc4181ddd26a16d83</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904651/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904651/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2664744$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9158112$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>RIDINGS, J.</creatorcontrib><creatorcontrib>NICHOLSON, I. C.</creatorcontrib><creatorcontrib>GOLDSWORTHY, W.</creatorcontrib><creatorcontrib>HASLAM, R.</creatorcontrib><creatorcontrib>ROBERTON, D. M.</creatorcontrib><creatorcontrib>ZOLA, H.</creatorcontrib><title>Somatic hypermutation of immunoglobulin genes in human neonates</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>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.</description><subject>affinity maturation</subject><subject>Amino Acid Sequence</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cloning, Molecular</subject><subject>Fetal Blood</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Genes, Immunoglobulin - genetics</subject><subject>Genes, Immunoglobulin - immunology</subject><subject>Genetics of the immune response</subject><subject>Humans</subject><subject>Immunobiology</subject><subject>immunoglobulin genes</subject><subject>immunoglobulin somatic mutation</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Infant</subject><subject>Infant, Newborn - immunology</subject><subject>Molecular Sequence Data</subject><subject>Mutation - immunology</subject><subject>neonatal antibody response</subject><subject>Nucleic Acid Heteroduplexes - immunology</subject><subject>Original</subject><subject>Sequence Analysis, DNA</subject><issn>0009-9104</issn><issn>1365-2249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><recordid>eNqVUU1v1DAQtRCobFt-AlKEELcEj2NP1hxAaNXSSpU4tHfLcZxdrxJ7iRPo_nscNVrgVHGyR-9Db-YR8g5oAZTjx30BJYqcMS4LkLIqSiyBIS8eX5DVCXpJVpRSmcukeU3OY9ynERHZGTmTINYAbEW-3Idej85ku-PBDv00piH4LLSZ6_vJh20X6qlzPttab2OWPrup1z7zNng92nhJXrW6i_bN8l6Qh-urh81Nfvf92-3m611ukLIy1wLLtrSCWwBtdcMZFcLUFZq6MaK2pq6loLhumdGVlI3hsIamaRhqwGZdXpDPT7aHqe5tY6wfB92pw-B6PRxV0E79i3i3U9vwU4FMBxOQDD4sBkP4Mdk4qt5FY7tOp02mqCqZYiLKZ4mAVHBKZ8dPT0QzhBgH257SAFVzTWqv5i7U3IWaa1JLTeoxid_-vc9JuvSS8PcLrqPRXTtob1w80Rgirzj_c5ZfrrPH_wigNle3aSh_A6x7sC8</recordid><startdate>199705</startdate><enddate>199705</enddate><creator>RIDINGS, J.</creator><creator>NICHOLSON, I. C.</creator><creator>GOLDSWORTHY, W.</creator><creator>HASLAM, R.</creator><creator>ROBERTON, D. M.</creator><creator>ZOLA, H.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Blackwell Science Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>199705</creationdate><title>Somatic hypermutation of immunoglobulin genes in human neonates</title><author>RIDINGS, J. ; NICHOLSON, I. C. ; GOLDSWORTHY, W. ; HASLAM, R. ; ROBERTON, D. M. ; ZOLA, H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6023-a563f3e54e11aead42055cb76cbdc5becbb95068f2ca799dc4181ddd26a16d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>affinity maturation</topic><topic>Amino Acid Sequence</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Cloning, Molecular</topic><topic>Fetal Blood</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Genes, Immunoglobulin - genetics</topic><topic>Genes, Immunoglobulin - immunology</topic><topic>Genetics of the immune response</topic><topic>Humans</topic><topic>Immunobiology</topic><topic>immunoglobulin genes</topic><topic>immunoglobulin somatic mutation</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Infant</topic><topic>Infant, Newborn - immunology</topic><topic>Molecular Sequence Data</topic><topic>Mutation - immunology</topic><topic>neonatal antibody response</topic><topic>Nucleic Acid Heteroduplexes - immunology</topic><topic>Original</topic><topic>Sequence Analysis, DNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>RIDINGS, J.</creatorcontrib><creatorcontrib>NICHOLSON, I. C.</creatorcontrib><creatorcontrib>GOLDSWORTHY, W.</creatorcontrib><creatorcontrib>HASLAM, R.</creatorcontrib><creatorcontrib>ROBERTON, D. M.</creatorcontrib><creatorcontrib>ZOLA, H.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>RIDINGS, J.</au><au>NICHOLSON, I. C.</au><au>GOLDSWORTHY, W.</au><au>HASLAM, R.</au><au>ROBERTON, D. M.</au><au>ZOLA, H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Somatic hypermutation of immunoglobulin genes in human neonates</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>1997-05</date><risdate>1997</risdate><volume>108</volume><issue>2</issue><spage>366</spage><epage>374</epage><pages>366-374</pages><issn>0009-9104</issn><eissn>1365-2249</eissn><coden>CEXIAL</coden><abstract>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.</abstract><cop>Oxford BSL</cop><pub>Blackwell Science Ltd</pub><pmid>9158112</pmid><doi>10.1046/j.1365-2249.1997.3631264.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical and experimental immunology, 1997-05, Vol.108 (2), p.366-374 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1904651 |
| source | Open Access: PubMed Central |
| 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 |
| title | Somatic hypermutation of immunoglobulin genes in human neonates |
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