Kabrani Eleni, Rahjouei Ali, Berruezo-Llacuna Maria, Ebeling Svenja, Saha Tannishtha, Altwasser Robert, Delgado-Benito Veronica, Pavri Rushad, Di Virgilio Michela
Laboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany.
Department of Anesthesiology and Intensive Care Medicine, and Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.
Nat Commun. 2025 Jan 17;16(1):777. doi: 10.1038/s41467-025-56166-5.
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.
保护性免疫反应的建立依赖于终末分化B细胞分泌具有不同效应功能的多种抗原特异性抗体的能力。RIF1是一种多功能蛋白，在类别转换重组过程中，它通过其DNA末端保护活性促进抗体同种型多样化。在本研究中，我们发现RIF1缺失导致体外浆母细胞形成增加，并在免疫后增强向浆细胞的终末分化。从机制上讲，这种表型独立于RIF1在DNA修复和类别转换重组中的作用，反映了其调节一部分BLIMP1靶基因转录状态的能力。因此，我们在此表明，除了促进抗体多样化外，RIF1还微调晚期B细胞分化的动力学，从而在体液免疫的建立中提供额外的调控层次。
