RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses
Abstract The establishment of protective immune responses relies on the ability of terminally differentiated B cells to secrete a broad variety of antigen-specific antibodies with different effector functions. RIF1 is a multifunctional protein that promotes antibody isotype diversification via its D...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56166-5 |
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| author | Eleni Kabrani Ali Rahjouei Maria Berruezo-Llacuna Svenja Ebeling Tannishtha Saha Robert Altwasser Veronica Delgado-Benito Rushad Pavri Michela Di Virgilio |
| author_facet | Eleni Kabrani Ali Rahjouei Maria Berruezo-Llacuna Svenja Ebeling Tannishtha Saha Robert Altwasser Veronica Delgado-Benito Rushad Pavri Michela Di Virgilio |
| author_sort | Eleni Kabrani |
| collection | DOAJ |
| description | Abstract The establishment of protective immune responses relies on the ability of terminally differentiated B cells to secrete a broad variety of antigen-specific antibodies with different effector functions. RIF1 is a multifunctional protein that promotes antibody isotype diversification via its DNA end protection activity during class switch recombination. In this study, we showed that RIF1 ablation resulted in increased plasmablast formation ex vivo and enhanced terminal differentiation into plasma cells upon immunization. Mechanistically, this phenotype is independent from RIF1’s role in DNA repair and class switch recombination, and reflects its ability to modulate the transcriptional status of a subset of BLIMP1 target genes. Therefore, here we show that, in addition to promoting antibody diversification, RIF1 fine-tunes the kinetics of late B cell differentiation, thus providing an additional layer of control in the establishment of humoral immunity. |
| format | Article |
| id | doaj-art-c263a770e18a4cdca311e06705c5fed5 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c263a770e18a4cdca311e06705c5fed52025-01-19T12:30:55ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-025-56166-5RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responsesEleni Kabrani0Ali Rahjouei1Maria Berruezo-Llacuna2Svenja Ebeling3Tannishtha Saha4Robert Altwasser5Veronica Delgado-Benito6Rushad Pavri7Michela Di Virgilio8Laboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationLaboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationLaboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationLaboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationLaboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationLaboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationLaboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationPeter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King’s College LondonLaboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationAbstract The establishment of protective immune responses relies on the ability of terminally differentiated B cells to secrete a broad variety of antigen-specific antibodies with different effector functions. RIF1 is a multifunctional protein that promotes antibody isotype diversification via its DNA end protection activity during class switch recombination. In this study, we showed that RIF1 ablation resulted in increased plasmablast formation ex vivo and enhanced terminal differentiation into plasma cells upon immunization. Mechanistically, this phenotype is independent from RIF1’s role in DNA repair and class switch recombination, and reflects its ability to modulate the transcriptional status of a subset of BLIMP1 target genes. Therefore, here we show that, in addition to promoting antibody diversification, RIF1 fine-tunes the kinetics of late B cell differentiation, thus providing an additional layer of control in the establishment of humoral immunity.https://doi.org/10.1038/s41467-025-56166-5 |
| spellingShingle | Eleni Kabrani Ali Rahjouei Maria Berruezo-Llacuna Svenja Ebeling Tannishtha Saha Robert Altwasser Veronica Delgado-Benito Rushad Pavri Michela Di Virgilio RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses Nature Communications |
| title | RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses |
| title_full | RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses |
| title_fullStr | RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses |
| title_full_unstemmed | RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses |
| title_short | RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses |
| title_sort | rif1 integrates dna repair and transcriptional requirements during the establishment of humoral immune responses |
| url | https://doi.org/10.1038/s41467-025-56166-5 |
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