The H2B deubiquitinase Usp22 promotes antibody class switch recombination by facilitating non-homologous end joining

Conglei Li, Thergiory Irrazabal, Clare C. So, Maribel Berru, Likun Du, Evelyn Lam, Alexanda K. Ling, Jennifer L. Gommerman, Qiang Pan-Hammarström and Alberto Martin ()
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Conglei Li: University of Toronto
Thergiory Irrazabal: University of Toronto
Clare C. So: University of Toronto
Maribel Berru: University of Toronto
Likun Du: Karolinska Institutet
Evelyn Lam: University of Toronto
Alexanda K. Ling: University of Toronto
Jennifer L. Gommerman: University of Toronto
Qiang Pan-Hammarström: Karolinska Institutet
Alberto Martin: University of Toronto

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Class switch recombination (CSR) has a fundamental function during humoral immune response and involves the induction and subsequent repair of DNA breaks in the immunoglobulin (Ig) switch regions. Here we show the role of Usp22, the SAGA complex deubiquitinase that removes ubiquitin from H2B-K120, in the repair of programmed DNA breaks in vivo. Ablation of Usp22 in primary B cells results in defects in γH2AX and impairs the classical non-homologous end joining (c-NHEJ), affecting both V(D)J recombination and CSR. Surprisingly, Usp22 depletion causes defects in CSR to various Ig isotypes, but not IgA. We further demonstrate that IgG CSR primarily relies on c-NHEJ, whereas CSR to IgA is more reliant on the alternative end joining pathway, indicating that CSR to different isotypes involves distinct DNA repair pathways. Hence, Usp22 is the first deubiquitinase reported to regulate both V(D)J recombination and CSR in vivo by facilitating c-NHEJ.

Date: 2018
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DOI: 10.1038/s41467-018-03455-x

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