Molecular analysis of γ1, γ3, and α class switch recombination junctions in APOBEC3-deficient mice using high-throughput sequencing

Issaoui, Hussein; Ferrad, Mélissa; Ghazzaui, Nour; Lecardeur, Sandrine; Cook-Moreau, Jeanne; Boyer, François; Denizot, Yves

doi:10.1038/s41423-019-0301-6

Cited by 2 publications

(2 citation statements)

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“…WR C and SY C -motif mutations both have been associated with AID-induced mutations of the immunoglobulin variable region genes, with mutations in WR C motifs being much more common (62). Although AID is known to be responsible for antibody affinity maturation in germinal center B cells, AID-catalyzed somatic hypermutation and class-switch recombination also have been demonstrated in immature B cells (61).…”

Section: Discussionmentioning

confidence: 99%

“…Although ATC-motif mutations have been attributed to mA3 from in vitro experiments (50), the differences in their distributions in the absence of Rem and in different mouse strains suggest that cytidine mutations within ATC and TYC sequences result from independent enzymes. WRC and SYC-motif mutations both have been associated with AID-induced mutations of the immunoglobulin variable region genes, with mutations in WRC motifs being much more common (62). Although AID is known to be responsible for antibody affinity maturation in germinal center B cells, AID-catalyzed somatic hypermutation and class-switch recombination also have been demonstrated in immature B cells (61).…”

Section: Discussionmentioning

confidence: 99%

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Apobec-Mediated Retroviral HypermutationIn Vivois Dependent on Mouse Strain

Byun,

Singh,

et al. 2023

Preprint

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Replication of the complex retrovirus mouse mammary tumor virus (MMTV) is antagonized by murine Apobec3 (mA3), a member of the Apobec family of cytidine deaminases. We have shown that MMTV-encoded Rem protein inhibits proviral mutagenesis by the Apobec enzyme, activation-induced cytidine deaminase (AID) during viral replication in BALB/c mice. To further study the role of Remin vivo, we have infected C57BL/6 (B6) mice with a superantigen-independent lymphomagenic strain of MMTV (TBLV-WT) or a mutant strain (TBLV-SD) that is defective in Rem and its cleavage product Rem-CT. Unlike MMTV, TBLV induced T-cell tumors in µMT mice, indicating that mature B cells, which express the highest AID levels, are not required for TBLV replication. Compared to BALB/c, B6 mice were more susceptible to TBLV infection and tumorigenesis. The lack of Rem expression accelerated B6 tumorigenesis at limiting doses compared to TBLV-WT in either wild-type B6 or AID-deficient mice. However, unlike proviruses from BALB/c mice, high-throughput sequencing indicated that proviral G-to-A or C-to-T changes did not significantly differ in the presence and absence of Rem expression.Ex vivostimulation showed higher levels of mA3 relative to AID in B6 compared to BALB/c splenocytes, but effects of agonists differed in the two strains. RNA-Seq revealed increased transcripts related to growth factor and cytokine signaling in TBLV-SD-induced tumors relative to those from TBLV-WT, consistent with a third Rem function. Thus, Rem-mediated effects on tumorigenesis in B6 mice are independent of Apobec-mediated proviral hypermutation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%