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Berruezo-Llacuna, M.

Publications and source records attributed to Berruezo-Llacuna, M..

2 recordsLinked to original sources
bioRxiv2023

RIF1 acts as a gatekeeper of B cell identity during late differentiation

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 (CSR). In this study, we showed that RIF1 ablation resulted in increased plasmablast (PB) formation ex vivo and enhanced terminal differentiation into plasma cells (PCs) upon immunization. Mechanistically, this phenotype is independent from RIF1s role in DNA repair and CSR, and reflects its ability to modulate the transcriptional status of a subset of BLIMP1 target genes. Therefore, in addition to promoting antibody isotype diversification, RIF1 fine-tunes the kinetics of late B cell differentiation, thus providing an additional layer of control in the establishment of humoral immunity.

immunology↗
bioRxiv2020

Pdap1 protects mature B lymphocytes from stress-induced cell death and promotes antibody gene diversification

The establishment of protective humoral immunity is dependent on the ability of mature B cells to undergo antibody gene diversification while adjusting to the physiological stressors induced by activation with the antigen. Mature B cells diversify their antibody genes by class switch recombination (CSR) and somatic hypermutation (SHM), which are both dependent on efficient induction of activation-induced cytidine deaminase (AID). Here, we identified PDGFA-associated protein 1 (Pdap1) as an essential regulator of cellular homeostasis in mature B cells. Pdap1 deficiency leads to sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and defective AID expression. As a consequence, loss of Pdap1 reduces germinal center B cell formation and impairs CSR and SHM. Thus, Pdap1 protects mature B cells against chronic ISR activation and ensures efficient antibody diversification by promoting their survival and optimal function.

immunology↗