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Controlling somatic hypermutation in immunoglobulin variable and switch regions

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Abstract

Activation-induced deaminase (AID) is a B-cell-specific enzyme required for initiating the mechanisms of affinity maturation and isotype switching of antibodies. AID functions by deaminating cytosine to uracil in DNA, which initiates a cascade of events resulting in mutations and strand breaks in the immunoglobulin loci. There is an intricate interplay between faithful DNA repair and mutagenic DNA repair during somatic hypermutation, in that some proteins from accurate repair pathways are also involved in mutagenesis. One factor that shifts the balance from faithful to mutagenic repair is the genomic sequence of the switch regions. Indeed, the sequence of the switch μ region is designed to maximize AID access to increase the abundance of clustered dU bases. The frequency and proximity of these dU nucleotides then in turn inhibit faithful repair and promote strand breaks.

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Acknowledgments

This research was supported by the Intramural Research Program of the NIH, National Institute on Aging.

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  1. Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA

    Robert W. Maul & Patricia J. Gearhart

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Correspondence to Patricia J. Gearhart.

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Maul, R.W., Gearhart, P.J. Controlling somatic hypermutation in immunoglobulin variable and switch regions. Immunol Res 47, 113–122 (2010). https://doi.org/10.1007/s12026-009-8142-5

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