Biology subjects

Kabrani, E.

Publications and source records attributed to Kabrani, E..

3 recordsLinked to original sources

bioRxiv2024

In vivo sequential mutagenesis in germinal center B cells using a dual-recombinase approach: FOXO1 re-expression upon FOXO1 knockout rescues class switch recombination

Modeling complex (patho)physiological processes by sequential mutagenesis in mice is limited by the lack of optimized genetic tools and complex breeding strategies. We present a new Cre/DreERT2 dual-recombinase germinal center B-cell (GCBC)- specific strain, with co-expression of the recombinases from a single allele. This enables highly efficient Cre-mediated FOXO1 knockout followed by time-controlled, efficient Dre-mediated FOXO1 re-expression and functional rescue in GCBCs, demonstrating suitability for precise targeted sequential mutagenesis in vivo.

immunology↗

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↗

bioRxiv2022

B cells are addicted to immunoglobulin production in the ER

Resting B cell dependence on the B cell antigen receptor (BCR) has been attributed solely to its signaling competence. We have recently shown that the presence of the BCR is vital for endoplasmic reticulum (ER) homeostasis and mitochondrial function both in primary B cells and Burkitt lymphoma (BL) cell lines. Unexpectedly, in BL Ramos cells this role has been shown to be independent of BCR signals from the cell membrane. Now, we provide evidence that also in mouse resting B cells ER-resident immunoglobulin (Ig) heavy chains control ER homeostasis, calcium storage and mitochondrial homeostasis through ER-mitochondria contacts. These findings demonstrate that BCR expression shapes cellular fitness already at the stage of assembly in the ER and uncover a new layer of B cell dependence on the production of Ig heavy chains in the ER. Sensing protein expression in the ER, with counterselection of compromised cells, might well operate also in other differentiated cells.

immunology↗