- 同
- SHM
PrepTutorEJDIC
- 身体の / 体腔(たいこう)の / 体細胞の
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/12/19 11:08:11」(JST)
[Wiki en表示]
Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (eg. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM diversifies B cell receptors used to recognize foreign elements (antigens) and allows the immune system to adapt its response to new threats during the lifetime of an organism.[1] Somatic hypermutation involves a programmed process of mutation affecting the variable regions of immunoglobulin genes. Unlike germline mutation, SHM affects only individual immune cells, and the mutations are not transmitted to offspring.[2]
Mistargeted somatic hypermutation is a likely mechanism in the development of B-cell lymphomas.[3]
Contents
- 1 Targeting
- 2 Mechanisms
- 3 See also
- 4 References
- 5 External links
Targeting
When a B cell recognizes an antigen, it is stimulated to divide (or proliferate). During proliferation, the B cell receptor locus undergoes an extremely high rate of somatic mutation that is at least 105-106 fold greater than the normal rate of mutation across the genome.[2] Variation is mainly in the form of single base substitutions, with insertions and deletions being less common. These mutations occur mostly at “hotspots” in the DNA, known as hypervariable regions. These regions correspond to the complementarity determining regions; the sites involved in antigen recognition on the immunoglobulin.[4] The exact nature of this targeting is poorly understood, although is thought to be controlled by a balance of error-prone and high fidelity repair.[5] This directed hypermutation allows for the selection of B cells that express immunoglobulin receptors possessing an enhanced ability to recognize and bind a specific foreign antigen.[1]
Mechanisms
Chemical structure of cytosine
Chemical structure of uracil
Experimental evidence supports the view that the mechanism of SHM involves deamination of cytosine to uracil in DNA by an enzyme called Activation-Induced (Cytidine) Deaminase, or AID.[6][7] A cytosine:guanine pair is thus directly mutated to a uracil:guanine mismatch. Uracil residues are not normally found in DNA, therefore, to maintain the integrity of the genome most of these mutations must be repaired by high-fidelity DNA mismatch repair enzymes. The uracil bases are removed by the repair enzyme, uracil-DNA glycosylase.[7] Error-prone DNA polymerases are then recruited to fill in the gap and create mutations.[6][8]
The synthesis of this new DNA involves error-prone DNA polymerases, which often introduce mutations either at the position of the deaminated cytosine itself or neighboring base pairs. During B cell division the immunoglobulin variable region DNA is transcribed and translated. The introduction of mutations in the rapidly proliferating population of B cells ultimately culminates in the production of thousands of B cells, possessing slightly different receptors and varying specificity for the antigen, from which the B cell with highest affinities for the antigen can be selected. The B cells with the greatest affinity will then be selected to differentiate into plasma cells producing antibody and long-lived memory B cells contributing to enhanced immune responses upon reinfection.[2]
The hypermutation process also utilizes cells that auto-select against the 'signature' of an organism's own cells. It is hypothesized that failures of this auto-selection process may also lead to the development of an auto-immune response.
See also
- Affinity maturation
- Anergy
- Immune system
- V(D)J recombination
References
- ^ a b Janeway, C.A., Travers, P., Walport, M., Shlomchik, M.J. (2005). Immunobiology (6th ed.). Garland Science. ISBN 0-8153-4101-6.
- ^ a b c Oprea, M. (1999) Antibody Repertoires and Pathogen Recognition: The Role of Germline Diversity and Somatic Hypermutation (Thesis) University of Leeds.
- ^ Odegard V.H., Schatz D.G. (2006). "Targeting of somatic hypermutation". Nat. Rev. Immunol. 6 (8): 573–583. doi:10.1038/nri1896. PMID 16868548.
- ^ Li, Z., Wool, C.J., Iglesias-Ussel, M.D., Ronai, D., and Scharff, M.D. (2004). "The generation of antibody diversity through somatic hypermutation and class switch recombination". Genes & Development 18 (1): 1–11. doi:10.1101/gad.1161904. PMID 14724175.
- ^ Liu, M., Schatz, D.G. (2009). "Balancing AID and DNA repair during somatic hypermutation. Trends in Immunology". Trends in Immunology 30 (4): 173–181. doi:10.1016/j.it.2009.01.007. PMID 19303358.
- ^ a b Teng, G. and Papavasiliou, F.N. (2007). "Immunoglobulin Somatic Hypermutation". Annu. Rev. Genet. 41: 107–120. doi:10.1146/annurev.genet.41.110306.130340. PMID 17576170.
- ^ a b Larson, E.D. and Maizels, N. (2004). "Transcription-coupled mutagenesis by the DNA deaminase AID". Genome Biol. 5 (3): 211. doi:10.1186/gb-2004-5-3-211. PMC 395756. PMID 15003109.
- ^ Bachl, J., Ertongur, I., Jungnickel, B. (2006). "Involvement of Rad18 in somatic hypermutation". Proc. Natl. Acad. Sci. USA 103 (32): 12081–86. doi:10.1073/pnas.0605146103.
External links
- Immunoglobulin somatic hypermutation at the US National Library of Medicine Medical Subject Headings (MeSH)
|
Immunology: Lymphocytic adaptive immune system and complement
|
|
| Lymphoid |
|
Antigens
|
- Antigen presentation/Professional APCs: Dendritic cell
- Macrophage
- B cell
- Immunogen
|
|
|
Antibodies
|
- Antibody
- Monoclonal antibodies
- Polyclonal antibodies
- Autoantibody
- Microantibody
- Polyclonal B cell response
- Allotype
- Isotype
- Idiotype
|
|
|
Immunity vs.
tolerance
|
- action: Immunity
- Autoimmunity
- Alloimmunity
- Allergy
- Hypersensitivity
- Inflammation
- Cross-reactivity
- inaction: Tolerance
- Central
- Peripheral
- Clonal anergy
- Clonal deletion
- Tolerance in pregnancy
- Immunodeficiency
|
|
|
Immunogenetics
|
- Affinity maturation (Somatic hypermutation
- Clonal selection)
- V(D)J recombination
- Junctional diversity
- Immunoglobulin class switching
- MHC/HLA
|
|
|
| Lymphocytes |
- Cellular (T cell)
- Humoral (B cell)
- NK cell
|
|
| Substances |
- Cytokines
- Opsonin
- Cytolysin
|
|
| Complement |
|
|
|
|
cell/phys/auag/auab/comp, igrc
|
|
|
|
|
|
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- High levels of AID cause strand bias of mutations at A versus T in Burkitt's lymphoma cells.
- Kano C, Wang JY.SourceLaboratory for Immune Diversity, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama 230-0045, Japan.
- Molecular immunology.Mol Immunol.2013 Jul;54(3-4):397-402. doi: 10.1016/j.molimm.2013.01.005. Epub 2013 Feb 9.
- Ig gene somatic hypermutation in the germinal center (GC) B cells occurs at C and G at roughly the same frequency. In contrast, there is a 2-fold increase of mutations at A relative to T on the non-transcribed strand of the V genes but it is unclear what triggers such strand bias. Using an efficient
- PMID 23399385
- Characterization of human anti-heat shock protein 60 monoclonal autoantibody Fab fragments in atherosclerosis: Genetic and functional analysis.
- Jang EJ, Jung KY, Hwang E, Jang YJ.SourceInstitute for Medical Science and Brain Korea 21 Program, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
- Molecular immunology.Mol Immunol.2013 Jul;54(3-4):338-46. doi: 10.1016/j.molimm.2012.12.013. Epub 2013 Jan 26.
- Heat shock protein 60 (HSP60) is an important autoantigen in atherosclerosis. The genetic structures and pathogenic roles of anti-HSP60 autoantibodies, however, have not been well elucidated. Here, we cloned nine monoclonal IgG Fabs against human HSP60 from peripheral blood lymphocytes of atheroscle
- PMID 23357787
- Molecular determinants of humoral immune specificity for the occupational allergen, methylene diphenyl diisocyanate.
- Wisnewski AV, Liu J.SourceDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8057, United States. adam.wisnewski@yale.edu
- Molecular immunology.Mol Immunol.2013 Jun;54(2):233-7. doi: 10.1016/j.molimm.2012.11.017. Epub 2013 Jan 4.
- Methylene diphenyl diisocyanate (MDI), a low molecular weight chemical important for producing polyurethane foam, coatings, and elastomers is a major cause of occupational asthma, however, mechanisms of disease pathogenesis remain poorly understood. This study characterizes the rearranged germline a
- PMID 23295252
Japanese Journal
- 免疫グロブリンの体細胞高頻度突然変異とserine/arginine-rich protein splicing factor (SRSF) (特集 免疫グロブリンの体細胞高頻度突然変異とクラススイッチ)
- 免疫グロブリンの体細胞高頻度突然変異とadenosine deaminase acting on RNA 1 (ADAR1) (特集 免疫グロブリンの体細胞高頻度突然変異とクラススイッチ)
- 免疫グロブリンの体細胞高頻度突然変異誘導とGANP (特集 免疫グロブリンの体細胞高頻度突然変異とクラススイッチ)
Related Links
- Our innovative platform is designed to replicate the natural process of somatic hypermutation (SHM) embedded within the human immune system to rapidly develop a diverse range of therapeutic-grade antibodies in vitro. SHM is a ...
- ... somatic hypermutation (SHM), class-switch recombination (CSR), and gene-conversion (GC). AID-catalyzed deamination of deoxycytidine creates a single nucleotide polymorphism (SNP) in the DNA strand by generating a : ...
Related Pictures
![Somatic hypermutation at A|[middot]|T](https://1mg.info/0/b/w/2349.jpg)
★リンクテーブル★
[★]
- 英
- somatic hypermutation、somatic cell mutation、somatic mutation
- 関
- 体細胞変異、体細胞過剰変異、体細胞超変異
[★]
- 関
- somatic cell mutation、somatic hypermutation
[★]
- 関
- somatic hypermutation、somatic mutation
[★]
- 英
- somatic hypermutation
- 関
- 体細胞突然変異、体細胞超変異
[★]
- 同
- somatic hypermutation
[★]
- 関
- cell body、soma、somata、somatic cell、somatically
[★]