Targeting of somatic hypermutation.
Somatic hypermutation (SHM) introduces mutations in the variable region of immunoglobulin genes at a rate of approximately 10(-3) mutations per base pair per cell division, which is 10(6)-fold higher than the spontaneous mutation rate in somatic cells. To ensure genomic integrity, SHM needs to be targeted specifically to immunoglobulin genes. The rare mistargeting of SHM can result in mutations and translocations in oncogenes, and is thought to contribute to the development of B-cell malignancies. Despite years of intensive investigation, the mechanism of SHM targeting is still unclear. We review and attempt to reconcile the numerous and sometimes conflicting studies on the targeting of SHM to immunoglobulin loci, and highlight areas that hold promise for further investigation.
Odegard
Valerie H
VH
VaxInnate Corporation, 300 George Street, Suite 311, New Haven, Connecticut 06511, USA.
Schatz
David G
DG
D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology; D008957:Models, Genetic; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D006657:Histones; D007136:Immunoglobulins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase