Information AboutHypermutation |
| CATEGORIES ABOUT SOMATIC HYPERMUTATION | |
| immune system | |
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Mistargetted somatic hypermutation is currently under investigation as a possible mechanism in the development of B-cell Lymphoma s. Odegard VH, Schatz DG. Targeting of somatic hypermutation. ''Nat Rev Immunol'' 2006; 6(8): 573-83. PMID 16868548 TARGETS 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. The mutations that occur are mainly single base substitutions, with occasional insertions and deletions and occur at “hotspots” located throughout DNA that encodes the immunoglobulin variable region.Li, Ziqiang, Caroline J. Woo1, Maria D. Iglesias-Ussel, Diana Ronai and Matthew D. Scharff. (2004) ''The generation of antibody diversity through somatic hypermutation and class switch recombination'' Full Text (html) Genes & Development 18:1-11. 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 . MECHANISM Experimental evidence supports the view that the mechanism of SHM involves The synthesis of this new DNA involves error-prone DNA Polymerase s, which often introduce mutations either at the position of the deaminated cytosine itself or neighboring Base Pair s. 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 long-lived Plasma Cell s producing Antibody and Memory B Cell s contributing to enhanced immune responses upon reinfection. 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 REFERENCES EXTERNAL LINKS |
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