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- W4213024412 abstract "Abstract In B cells, IgD is expressed together with IgM through alternative splicing of primary V H DJ H -C μ -s-m-Cδ-s-m RNAs, and also through IgD class switch DNA recombination (CSR) via double-strand DNA breaks (DSB) and synapse of Sμ with σ δ . How such DSBs are resolved is still unknown, despite our previous report showing that Rad52 effects the ‘short-range’ microhomology-mediated synapsis of intra-Sμ region DSBs. Here we find that induction of IgD CSR downregulates Zfp318, and promotes Rad52 phosphorylation and recruitment to Sμ and σ δ , thereby leading to alternative end-joining (A-EJ)-mediated Sμ-σ δ recombination with extensive microhomologies, V H DJ H -C δ s transcription and sustained IgD secretion. Rad52 ablation in mouse Rad52 −/− B cells aborts IgD CSR in vitro and in vivo and dampens the specific IgD antibody response to OVA. Rad52 knockdown in human B cells also abrogates IgD CSR. Finally, Rad52 phosphorylation is associated with high levels of IgD CSR and anti-nuclear IgD autoantibodies in patients with systemic lupus erythematosus and in lupus-prone mice. Our findings thus show that Rad52 mediates IgD CSR through microhomology-mediated A-EJ in concert with Zfp318 downregulation." @default.
- W4213024412 created "2022-02-24" @default.
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- W4213024412 date "2022-02-21" @default.
- W4213024412 modified "2023-10-15" @default.
- W4213024412 title "Rad52 mediates class-switch DNA recombination to IgD" @default.
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- W4213024412 doi "https://doi.org/10.1038/s41467-022-28576-2" @default.
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