On the molecular mechanism of somatic hypermutation of rearranged immunoglobulin genes.
Somatic hypermutation (SHM) diversifies the genes that encode immunoglobulin variable regions in antigen-activated germinal centre B lymphocytes. Available evidence strongly suggests that DNA deamination potentiates phase I SHM and subsequently triggers phase II SHM. A concise review of this evidence is followed by a detailed critique of two possible models which suggest that polymerase-eta potentiates phase II SHM via either its DNA-dependent or its RNA-dependent DNA synthetic activity. Quantitative analysis, in the context of extant data that define the features of SHM, favours the RNA-dependent mechanism.
Franklin
Andrew
A
Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia. Andrew.Franklin@anu.edu.au
Blanden
Robert V
RV
D000818:Animals; D015321:Gene Rearrangement / Q000235:genetics*; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*