RNA helicase DDX1 regulates germinal centre selection and affinity maturation by promoting tRNA ligase activity
Kimber, R.; Ingelsfield, S.; Screen, M.; Salerno, F.; Matheson, L. S.; Okkenhaug, H.; Whale, A.; Assalaarachchi, J.; Stammers, M.; Akdeniz, D.; Andrews, S.; Ribeiro de Almeida, C.
Show abstract
Clonal expansion of antigen-specific B-cells defines effective germinal centre responses and is key for the generation of high-affinity antibodies. While positive selection in germinal centres has been associated with anabolic metabolism and cell growth, the downstream drivers of B-cell proliferation are not well understood. Here we report that the RNA helicase DDX1 is required for germinal centre maturation and accrual of dark-zone cellularity. Upon interaction with T-follicular helper cells, DDX1-deficient B-cells upregulate c-MYC but do not clonally expand. We show that positive selection is coupled with an increase in mRNA translation, that is dependent on DDX1. DDX1 endows B-cells with the protein biosynthetic capability that is required for rapid cell proliferation. It does so by modulating the activity of the tRNA ligase complex and tRNA splicing. Our data reveal that mRNA translation efficiency is a key determinant of B-cell fitness during germinal centre responses.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Rad52 mediates class-switch DNA recombination to IgD 97%
- An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells 97%
- Cooperative super-enhancer inactivation caused by heterozygous loss of CREBBP and KMT2D skews B cell fate decisions and yields T cell-depleted lymphomas 97%
Similar papers in this journal
- Negative feedback by NUR77/Nr4a1 restrains B cell clonal dominance during early T-dependent immune responses 96%
- STAT3 signaling in B cells controls germinal center zone organization and recycling 96%
- Uncontrolled CD21low age-associated and B1 B cell accumulation caused by failure of an EGR2/3 tolerance checkpoint 95%
Similar papers in this journal
- The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development 97%
- A negative feedback loop mediated by the NR4A family of nuclear hormone receptors restrains expansion of B cells that receive signal one in the absence of signal two 97%
- Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program 95%
Similar papers in this journal
- An Interleukin 9-Zbtb18 axis promotes germinal center development of memory B cells 97%
- Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation. 97%
- Opposing effects of pre-existing antibody and memory T cell help on the dynamics of recall germinal centers 96%
Similar papers in this journal
- Galectin-9 regulates the threshold of B cell activation and autoimmunity 97%
- SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire 96%
- The Structure-Selective Endonucleases GEN1 and MUS81 are Functionally Complementary in Safeguarding the Genome of Proliferating B Lymphocytes 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.