「体細胞超変異」の版間の差分

{{翻訳直後|[[:en:Special:Redirect/revision/1001956154|en:Somatic hypermutation]]|date=2021年2月}}

'''体細胞超変異'''（たいさいぼうちょうへんい、{{Lang-en-short|Somatic hypermutation, '''SHM'''}}）もしくは'''体細胞超突然変異'''（たいさいぼうちょうとつぜんへんい）とは、{{仮リンク|適応免疫系|en|Adaptive immune system}}が[[微生物]]などの新しい外来要素に適応する手段の1つで、[[クラススイッチ]]の際などに見られる[[細胞]]メカニズムである。{{仮リンク|親和性成熟|en|Affinity maturation}}の中でも重要な一部であり、外来要素（[[抗原]]）を認識するために使用される[[B細胞]]受容体を多様化し、免疫系が生物個体の一生を通じて新しい脅威へ適応可能とする<ref name="Janeway2005">{{Cite book|last=Janeway, C.A.|last2=Travers, P.|last3=Walport, M.|last4=Shlomchik, M.J.|year=2005|title=Immunobiology|edition=6th|publisher=Garland Science|isbn=978-0-8153-4101-7}}</ref>。[[抗体|免疫グロブリン]]遺伝子の可変領域に影響を与えるプログラム済み[[突然変異]]を伴う。{{仮リンク|生殖細胞系列変異|en|Germline mutation}}とは異なり、SHMは生物の個々の[[リンパ球|免疫細胞]]にのみ影響を及ぼし、子孫に遺伝することはない<ref name="Oprea1999">Oprea, M. (1999) [http://www.santafe.edu/~mihaela/thesis/version_short.html ''Antibody Repertoires and Pathogen Recognition:''] {{Webarchive|url=https://web.archive.org/web/20080906130252/http://www.santafe.edu/~mihaela/thesis/version_short.html|date=2008-09-06}} The Role of Germline Diversity and Somatic Hypermutation'' (Thesis) University of Leeds.''</ref>。{{仮リンク|B細胞リンパ腫|en}}<ref name="Odegard2006">{{Cite journal|last=Odegard V.H.|last2=Schatz D.G.|year=2006|title=Targeting of somatic hypermutation|journal=Nat. Rev. Immunol.|volume=6|issue=8|pages=573–583|DOI=10.1038/nri1896|PMID=16868548}}</ref>その他の多くの癌<ref name=":18">{{Cite journal|last=Steele|first=E.J.|last2=Lindley|first2=R.A.|year=2010|title=Somatic mutation patterns in non-lymphoid cancers resemble the strand biased somatic hypermutation spectra of antibody genes|url=http://researchrepository.murdoch.edu.au/id/eprint/4482/1/Somatic_mutation_patterns.pdf|journal=DNA Repair|volume=9|issue=6|pages=600–603|DOI=10.1016/j.dnarep.2010.03.007|PMID=20418189}}</ref><ref name=":19">{{Cite journal|last=Lindley|first=R.A.|last2=Steele|first2=E.J.|year=2013|title=Critical analysis of strand-biased somatic mutation signatures in TP53 versus Ig genes, in genome -wide data and the etiology of cancer|url=https://www.hindawi.com/journals/isrn/2013/921418/|journal=ISRN Genomics|volume=2013 Article ID 921418|pages=18 pages}}</ref>の発症にメカニズムに誤標的化体細胞超変異が関わっている可能性が高い。

 

超変異プロセスは、生物個体自身の細胞の'signature'{{訳語疑問点|date=2021年2月}}に対して自己選択する細胞も利用する。この自己選択プロセスの失敗が{{仮リンク|自己免疫|en|Autoimmunity}}反応の発生につながるという仮説がある<ref>{{Cite journal|last=Metzger|first=T.C.|year=2011|title=Control of Central and Peripheral Tolerance by Aire|journal=Immunol Rev. 2011 May|volume=241|issue=1|pages=89–103|DOI=10.1111/j.1600-065X.2011.01008.x|PMID=21488892|PMC=3093413}}</ref>。

 

== モデル ==

Developments on the viability of the two main competing molecular models on the mechanism of somatic hypermutation (SHM) since 1987 have now reached a resolution, particular molecular data published since 2000.

Much of this early phase data has been reviewed by Teng and Papavasiliou<ref name="Teng2007">{{Cite journal|last=Teng, G.|last2=Papavasiliou, F.N.|year=2007|title=Immunoglobulin Somatic Hypermutation|journal=Annu. Rev. Genet.|volume=41|pages=107–120|DOI=10.1146/annurev.genet.41.110306.130340|PMID=17576170}}</ref> and additionally outlined by Di Noia and Maul,<ref name=":3">{{Cite journal|last=Di Noia|first=J. M.|last2=Neuberger|first2=M. S.|date=2007|title=Molecular mechanisms of somatic hypermutation|journal=Annu. Rev. Biochem.|volume=76|pages=1–22|DOI=10.1146/annurev.biochem.76.061705.090740|PMID=17328676}}</ref><ref name=":4">{{Cite book|last=Maul|first=R. W.|last2=Gearhart|first2=P. J.|title=AID and Somatic Hypermutation|journal=Adv. Immunol|volume=105|pages=159–191|date=2010|doi=10.1016/S0065-2776(10)05006-6|pmid=20510733|pmc=2954419|series=Advances in Immunology|isbn=9780123813022}}</ref> and the SHM field data reviewed in Steele<ref name=":0">{{Cite journal|last=Steele|first=E.J.|year=2016|title=Somatic hypermutation in immunity and cancer: Critical analysis of strand-biased and codon-context mutation signatures.|journal=DNA Repair|volume=45|pages=1–24|DOI=10.1016/j.dnarep.2016.07.001|PMID=27449479}}</ref><ref name=":20">{{Cite journal|last=Steele|first=E.J.|last2=Pollard|first2=J.W.|year=1987|title=Hypothesis : Somatic Hypermutation by gene conversion via the error prone DNA-to-RNA-to-DNA information loop|journal=Mol. Immunol.|volume=24|issue=6|pages=667–673|DOI=10.1016/j.dnarep.2016.07.001|PMID=2443841}}</ref> and additionally outlined in these papers.<ref name=":18">{{Cite journal|last=Steele|first=E.J.|last2=Lindley|first2=R.A.|year=2010|title=Somatic mutation patterns in non-lymphoid cancers resemble the strand biased somatic hypermutation spectra of antibody genes|url=http://researchrepository.murdoch.edu.au/id/eprint/4482/1/Somatic_mutation_patterns.pdf|journal=DNA Repair|volume=9|issue=6|pages=600–603|DOI=10.1016/j.dnarep.2010.03.007|PMID=20418189}}</ref><ref name=":19">{{Cite journal|last=Lindley|first=R.A.|last2=Steele|first2=E.J.|year=2013|title=Critical analysis of strand-biased somatic mutation signatures in TP53 versus Ig genes, in genome -wide data and the etiology of cancer|url=https://www.hindawi.com/journals/isrn/2013/921418/|journal=ISRN Genomics|volume=2013 Article ID 921418|pages=18 pages}}</ref><ref name=":10">{{Cite journal|last=Steele|first=E.J.|last2=Lindley|first2=R.A.|last3=Wen|first3=J|last4=Weiler|first4=G.F.|year=2006|title=Computational analyses show A-to-G mutations correlate with nascent mRNA hairpins at somatic hypermutation hotspots.|journal=DNA Repair|volume=5|issue=11|pages=1346–1363|DOI=10.1016/j.dnarep.2006.06.002|PMID=16884961}}</ref><ref name=":11">{{Cite journal|last=Steele|first=E.J.|last2=Franklin|first2=A|last3=Blanden|first3=R.V.|year=2004|title=Genesis of the strand biased signature in somatic hypermutation of rearranged immunoglobulin variable genes.|journal=Immunol. Cell Biol.|volume=82|issue=2|pages=208–218|DOI=10.1046/j.0818-9641.2004.01224.x|PMID=15061776}}</ref><ref name=":12">{{Cite journal|last=Franklin|first=A.|last2=Milburn|first2=P. J.|last3=Blanden|first3=R.V.|last4=Steele|first4=E. J.|date=2004|title=Human DNA polymerase-eta an A-T mutator in somatic hypermutation of rearranged immunoglobulin genes, is a reverse transcriptase|journal=Immunol. Cell Biol.|volume=82|issue=2|pages=219–225|DOI=10.1046/j.0818-9641.2004.01221.x|PMID=15061777}}</ref><ref name=":13">{{Cite journal|last=Steele|first=E.J.|year=2009|title=Mechanism of somatic hypermutation: Critical analysis of strand biased mutation signatures at A:T and G:C base pairs.|journal=Mol. Immunol.|volume=46|issue=3|pages=305–320|DOI=10.1016/j.molimm.2008.10.021|PMID=19062097}}</ref>

-->

 

== 関連項目 ==

 

* [[V(D)J遺伝子再構成]]

* [[クラススイッチ]]

 

== 外部リンク ==