Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting

Aged individuals, particularly males, display an impaired level of Ab response compared with their younger counterparts, yet the molecular mechanisms responsible for the discrepancy are not well understood. We hypothesize that some of this difference may be linked to B cell somatic hypermutation (SH...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Journal of immunology (1950) 2021-01, Vol.206 (1), p.101-108
Hauptverfasser: Cui, Ang, Chawla, Daniel G, Kleinstein, Steven H
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 108
container_issue 1
container_start_page 101
container_title The Journal of immunology (1950)
container_volume 206
creator Cui, Ang
Chawla, Daniel G
Kleinstein, Steven H
description Aged individuals, particularly males, display an impaired level of Ab response compared with their younger counterparts, yet the molecular mechanisms responsible for the discrepancy are not well understood. We hypothesize that some of this difference may be linked to B cell somatic hypermutation (SHM) targeting, including error-prone DNA repair activities that are crucial to Ab diversification. To examine the effects of aging on SHM targeting, we analyzed B cell Ig repertoire sequences from 27 healthy male and female human subjects aged 20-89. By studying mutation patterns based on 985,069 mutations obtained from 123,415 sequences, we found that the SHM mutability hierarchies on microsequence motifs (i.e., SHM hot/cold spots) are mostly consistent between different age and sex groups. However, we observed a lower frequency in mutations involving Phase II SHM DNA repair activities in older males, but not in females. We also observed, from a separate study, a decreased expression level of DNA mismatch repair genes involved in SHM in older individuals compared with younger individuals, with larger fold changes in males than in females. Finally, we showed that the balance between Phase I versus Phase II SHM activities impacts the resulting Ig phenotypes. Our results showed that the SHM process is altered in some older individuals, providing insights into observed clinical differences in immunologic responses between different age and sex groups.
doi_str_mv 10.4049/jimmunol.2000576
format Article
fullrecord <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_4049_jimmunol_2000576</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>33288546</sourcerecordid><originalsourceid>FETCH-LOGICAL-c341t-3b0fa50f40ec98a52a384af09f6b2e2f2c122d8789a0251fb5b76d2419001ac93</originalsourceid><addsrcrecordid>eNo9kE1Lw0AQhhdRbK3ePcn-gdTZ2Y8kF6GWagsFD63nsNnshpTmg90E7L830tbT8DLvMzAPIc8M5gJE-nqo6npo2uMcAUDG6oZMmZQQKQXqlkwBECMWq3hCHkI4jB0FKO7JhHNMEinUlLzt7E_0XulgC7ooq6akK-es6QNtG7op6a6tdV8Zuj511tdDP4Zxsde-tP3YfiR3Th-DfbrMGfn-WO2X62j79blZLraR4YL1Ec_BaQlOgDVpoiVqngjtIHUqR4sODUMskjhJNaBkLpd5rAoULAVg2qR8RuB81_g2BG9d1vmq1v6UMcj-VGRXFdlFxYi8nJFuyGtb_APX3_kvdoRbOA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Cui, Ang ; Chawla, Daniel G ; Kleinstein, Steven H</creator><creatorcontrib>Cui, Ang ; Chawla, Daniel G ; Kleinstein, Steven H</creatorcontrib><description>Aged individuals, particularly males, display an impaired level of Ab response compared with their younger counterparts, yet the molecular mechanisms responsible for the discrepancy are not well understood. We hypothesize that some of this difference may be linked to B cell somatic hypermutation (SHM) targeting, including error-prone DNA repair activities that are crucial to Ab diversification. To examine the effects of aging on SHM targeting, we analyzed B cell Ig repertoire sequences from 27 healthy male and female human subjects aged 20-89. By studying mutation patterns based on 985,069 mutations obtained from 123,415 sequences, we found that the SHM mutability hierarchies on microsequence motifs (i.e., SHM hot/cold spots) are mostly consistent between different age and sex groups. However, we observed a lower frequency in mutations involving Phase II SHM DNA repair activities in older males, but not in females. We also observed, from a separate study, a decreased expression level of DNA mismatch repair genes involved in SHM in older individuals compared with younger individuals, with larger fold changes in males than in females. Finally, we showed that the balance between Phase I versus Phase II SHM activities impacts the resulting Ig phenotypes. Our results showed that the SHM process is altered in some older individuals, providing insights into observed clinical differences in immunologic responses between different age and sex groups.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.2000576</identifier><identifier>PMID: 33288546</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Aging - immunology ; B-Lymphocytes - immunology ; DNA Repair - genetics ; Female ; Humans ; Immunity, Humoral - physiology ; Immunoglobulins - genetics ; Male ; Middle Aged ; Mutation - genetics ; Sex Characteristics ; Sex Factors ; Somatic Hypermutation, Immunoglobulin ; Young Adult</subject><ispartof>The Journal of immunology (1950), 2021-01, Vol.206 (1), p.101-108</ispartof><rights>Copyright © 2020 by The American Association of Immunologists, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c341t-3b0fa50f40ec98a52a384af09f6b2e2f2c122d8789a0251fb5b76d2419001ac93</citedby><cites>FETCH-LOGICAL-c341t-3b0fa50f40ec98a52a384af09f6b2e2f2c122d8789a0251fb5b76d2419001ac93</cites><orcidid>0000-0001-7667-9337 ; 0000-0003-4957-1544 ; 0000-0002-1087-8568</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33288546$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cui, Ang</creatorcontrib><creatorcontrib>Chawla, Daniel G</creatorcontrib><creatorcontrib>Kleinstein, Steven H</creatorcontrib><title>Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Aged individuals, particularly males, display an impaired level of Ab response compared with their younger counterparts, yet the molecular mechanisms responsible for the discrepancy are not well understood. We hypothesize that some of this difference may be linked to B cell somatic hypermutation (SHM) targeting, including error-prone DNA repair activities that are crucial to Ab diversification. To examine the effects of aging on SHM targeting, we analyzed B cell Ig repertoire sequences from 27 healthy male and female human subjects aged 20-89. By studying mutation patterns based on 985,069 mutations obtained from 123,415 sequences, we found that the SHM mutability hierarchies on microsequence motifs (i.e., SHM hot/cold spots) are mostly consistent between different age and sex groups. However, we observed a lower frequency in mutations involving Phase II SHM DNA repair activities in older males, but not in females. We also observed, from a separate study, a decreased expression level of DNA mismatch repair genes involved in SHM in older individuals compared with younger individuals, with larger fold changes in males than in females. Finally, we showed that the balance between Phase I versus Phase II SHM activities impacts the resulting Ig phenotypes. Our results showed that the SHM process is altered in some older individuals, providing insights into observed clinical differences in immunologic responses between different age and sex groups.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging - immunology</subject><subject>B-Lymphocytes - immunology</subject><subject>DNA Repair - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Immunity, Humoral - physiology</subject><subject>Immunoglobulins - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation - genetics</subject><subject>Sex Characteristics</subject><subject>Sex Factors</subject><subject>Somatic Hypermutation, Immunoglobulin</subject><subject>Young Adult</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1Lw0AQhhdRbK3ePcn-gdTZ2Y8kF6GWagsFD63nsNnshpTmg90E7L830tbT8DLvMzAPIc8M5gJE-nqo6npo2uMcAUDG6oZMmZQQKQXqlkwBECMWq3hCHkI4jB0FKO7JhHNMEinUlLzt7E_0XulgC7ooq6akK-es6QNtG7op6a6tdV8Zuj511tdDP4Zxsde-tP3YfiR3Th-DfbrMGfn-WO2X62j79blZLraR4YL1Ec_BaQlOgDVpoiVqngjtIHUqR4sODUMskjhJNaBkLpd5rAoULAVg2qR8RuB81_g2BG9d1vmq1v6UMcj-VGRXFdlFxYi8nJFuyGtb_APX3_kvdoRbOA</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Cui, Ang</creator><creator>Chawla, Daniel G</creator><creator>Kleinstein, Steven H</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-7667-9337</orcidid><orcidid>https://orcid.org/0000-0003-4957-1544</orcidid><orcidid>https://orcid.org/0000-0002-1087-8568</orcidid></search><sort><creationdate>20210101</creationdate><title>Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting</title><author>Cui, Ang ; Chawla, Daniel G ; Kleinstein, Steven H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c341t-3b0fa50f40ec98a52a384af09f6b2e2f2c122d8789a0251fb5b76d2419001ac93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging - immunology</topic><topic>B-Lymphocytes - immunology</topic><topic>DNA Repair - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Immunity, Humoral - physiology</topic><topic>Immunoglobulins - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation - genetics</topic><topic>Sex Characteristics</topic><topic>Sex Factors</topic><topic>Somatic Hypermutation, Immunoglobulin</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cui, Ang</creatorcontrib><creatorcontrib>Chawla, Daniel G</creatorcontrib><creatorcontrib>Kleinstein, Steven H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cui, Ang</au><au>Chawla, Daniel G</au><au>Kleinstein, Steven H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>206</volume><issue>1</issue><spage>101</spage><epage>108</epage><pages>101-108</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Aged individuals, particularly males, display an impaired level of Ab response compared with their younger counterparts, yet the molecular mechanisms responsible for the discrepancy are not well understood. We hypothesize that some of this difference may be linked to B cell somatic hypermutation (SHM) targeting, including error-prone DNA repair activities that are crucial to Ab diversification. To examine the effects of aging on SHM targeting, we analyzed B cell Ig repertoire sequences from 27 healthy male and female human subjects aged 20-89. By studying mutation patterns based on 985,069 mutations obtained from 123,415 sequences, we found that the SHM mutability hierarchies on microsequence motifs (i.e., SHM hot/cold spots) are mostly consistent between different age and sex groups. However, we observed a lower frequency in mutations involving Phase II SHM DNA repair activities in older males, but not in females. We also observed, from a separate study, a decreased expression level of DNA mismatch repair genes involved in SHM in older individuals compared with younger individuals, with larger fold changes in males than in females. Finally, we showed that the balance between Phase I versus Phase II SHM activities impacts the resulting Ig phenotypes. Our results showed that the SHM process is altered in some older individuals, providing insights into observed clinical differences in immunologic responses between different age and sex groups.</abstract><cop>United States</cop><pmid>33288546</pmid><doi>10.4049/jimmunol.2000576</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-7667-9337</orcidid><orcidid>https://orcid.org/0000-0003-4957-1544</orcidid><orcidid>https://orcid.org/0000-0002-1087-8568</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0022-1767
ispartof The Journal of immunology (1950), 2021-01, Vol.206 (1), p.101-108
issn 0022-1767
1550-6606
language eng
recordid cdi_crossref_primary_10_4049_jimmunol_2000576
source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Adult
Aged
Aged, 80 and over
Aging - immunology
B-Lymphocytes - immunology
DNA Repair - genetics
Female
Humans
Immunity, Humoral - physiology
Immunoglobulins - genetics
Male
Middle Aged
Mutation - genetics
Sex Characteristics
Sex Factors
Somatic Hypermutation, Immunoglobulin
Young Adult
title Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T22%3A40%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sex-Biased%20Aging%20Effects%20on%20Ig%20Somatic%20Hypermutation%20Targeting&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Cui,%20Ang&rft.date=2021-01-01&rft.volume=206&rft.issue=1&rft.spage=101&rft.epage=108&rft.pages=101-108&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.2000576&rft_dat=%3Cpubmed_cross%3E33288546%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/33288546&rfr_iscdi=true