What Targets Somatic Hypermutation to the Immunoglobulin Loci?

Abstract:

:One of the most profound enigmas in B cell biology is how activation-induced deaminase (AID) is targeted to a very small region of DNA in the immunoglobulin loci. Two specific regions are singled out: the variable region of 2 kb that contains rearranged genes on the heavy, κ light, and λ light chain loci, and the switch region of ∼4 kb that contains an extensive stretch of G:C rich DNA on the heavy chain locus. Transcription is required for AID recruitment; however, many genes are also highly transcribed and do not undergo the catastrophic mutagenesis that occurs in variable and switch regions. The DNA sequences of these regions cause RNA polymerase II to accumulate for an extended distance of 2-4 kb. The stalled polymerases then recruit the transcription cofactor Spt5, and AID, which deaminates cytosines to uracils in exposed transcription bubbles. Thus, the immunoglobulin loci are unique in that a favorable combination of DNA sequences and 3' transcription enhancers make them the perfect storm for AID-induced somatic hypermutation.

journal_name

Viral Immunol

journal_title

Viral immunology

authors

Heltzel JMH,Gearhart PJ

doi

10.1089/vim.2019.0149

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

277-281

issue

4

eissn

0882-8245

issn

1557-8976

journal_volume

33

pub_type

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