On the molecular mechanism of somatic hypermutation of rearranged immunoglobulin genes

doi:doi:10.1111/j.1440-1711.2004.01289.x

Immunology and Cell Biology (2004) 82, 557–567; doi:10.1111/j.1440-1711.2004.01289.x

On the molecular mechanism of somatic hypermutation of rearranged immunoglobulin genes

Andrew Franklin¹ and Robert V Blanden¹

¹Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia

Correspondence: Dr Andrew Franklin, Biocontrol Group, School of Botany and Zoology, Australian National University, Daley Road, Acton, ACT 0200, Australia. Email: Andrew.Franklin@anu.edu.au

Received 31 May 2004; Accepted 14 July 2004.

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Abstract

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.