体细胞超突变

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AID可催化C脱氨转为U

体细胞超突变(英语:Somatic hypermutation,简称SHM)是脊椎动物免疫系统B细胞制造对抗原具高亲和力之抗体的一种机制,在B细胞于淋巴结生发中心进行亲合力成熟英语affinity maturation的过程中,透过活化诱导性胞苷脱氨酶(AID)与APOBEC3G等胞嘧啶脱氨酶诱导C脱氨U,进而启动碱基切除修复,由易误(error-prone)的DNA聚合酶η英语DNA polymerase eta完成修补而产生突变[1](也有观点认为C脱氨成U后可以mRNA反转录的方式进行DNA修补而造成突变[2]),增加B细胞制造的抗体多样性,其中制造抗体对抗原亲和力最高的B细胞会被免疫系统选择,分化成浆细胞记忆B细胞,使个体终生对该抗原具免疫力。体细胞超突变虽涉及DNA层级的改变,但并非生殖系突变,仅影响个别的B细胞而不会传给子代[3]。此机制的失控与B细胞淋巴瘤等多种癌症有关[4][5][6]

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  1. ^ Halemano K, Guo K, Heilman KJ, Barrett BS, Smith DS, Hasenkrug KJ; et al. 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 [2021-04-29]. PMID 20418189. doi:10.1016/j.dnarep.2010.03.007. (原始内容存档 (PDF)于2017-09-22). 
  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 [2021-04-29]. (原始内容存档于2021-05-01).