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體細胞超突變

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AID可催化C脫氨轉為U

體細胞超突變(Somatic hypermutation,簡稱SHM)是脊椎動物免疫系統B細胞製造對抗原具高親和力之抗體的一種機制,在B細胞於淋巴結生發中心進行親合力成熟英语affinity maturation的過程中,透過活化诱导性胞苷脱氨酶(AID)與APOBEC3G等胞嘧啶脫氨酶誘導C脫氨U,進而啟動鹼基切除修復,由易誤(error-prone)的DNA聚合酶η英语DNA polymerase eta完成修補而產生突變[1](也有觀點認為C脫氨成U後可以mRNA反轉錄的方式進行DNA修補而造成突變[2]),增加B細胞製造的抗體多樣性,其中製造抗體對抗原親和力最高的B細胞會被免疫系統選擇,分化成漿細胞記憶B細胞,使個體終生對該抗原具免疫力。體細胞超突變雖涉及DNA層級的改變,但並非生殖系突變,僅影響個別的B細胞而不會傳給子代[3]。此機制的失控與B細胞淋巴瘤等多種癌症有關[4][5][6]

參見[编辑]

參考文獻[编辑]

  1. ^ Halemano K, Guo K, Heilman KJ, Barrett BS, Smith DS, Hasenkrug KJ; 等. Immunoglobulin somatic hypermutation by APOBEC3/Rfv3 during retroviral infection.. Proc Natl Acad Sci U S A. 2014, 111 (21): 7759–64. PMC 4040588可免费查阅. PMID 24821801. doi:10.1073/pnas.1403361111. 
  2. ^ Steele EJ. Reverse Transcriptase Mechanism of Somatic Hypermutation: 60 Years of Clonal Selection Theory.. Front Immunol. 2017, 8: 1611. PMC 5704389可免费查阅. PMID 29218047. doi:10.3389/fimmu.2017.01611. 
  3. ^ Zan, Hong; Casali, Paolo. Immunoglobulin Somatic Hypermutation and Class-Switch DNA Recombination. Ian R. Mackay, Noel R. Rose, Betty Diamond, Anne Davidson (编). Encyclopedia of Medical Immunology. 2014: 517–528. doi:10.1007/978-0-387-84828-0_556. 
  4. ^ Odegard V.H.; Schatz D.G. Targeting of somatic hypermutation. Nat. Rev. Immunol. 2006, 6 (8): 573–583. PMID 16868548. doi:10.1038/nri1896. 
  5. ^ Steele, E.J.; Lindley, R.A. Somatic mutation patterns in non-lymphoid cancers resemble the strand biased somatic hypermutation spectra of antibody genes (PDF). DNA Repair. 2010, 9 (6): 600–603. PMID 20418189. doi:10.1016/j.dnarep.2010.03.007. 
  6. ^ Lindley, R.A.; Steele, E.J. Critical analysis of strand-biased somatic mutation signatures in TP53 versus Ig genes, in genome -wide data and the etiology of cancer. ISRN Genomics. 2013,. 2013 Article ID 921418: 18 pages.