Virus-like antigen display delivers a stand-alone danger signal through the BCR that circumvents tolerance
Riggs, J.; Ritter, A. J.; Bourassa, F. X. P.; Meyer, A. R.; Kay-Tsumagari, E.; Wholey, W.-Y.; Libang, J.; Mueller, J. L.; Lu, W.; Wingreen, N. S.; Cheng, W.; Zikherman, J.
Show abstract
How B cells discriminate self from foreign antigens remains a central question, given inherent autoreactivity of the mature B cell receptor (BCR) repertoire. Soluble antigen (sAg) induces tolerance, whereas patterned antigen display on virus-like particles (pAg) triggers robust B cell responses that can proceed without T cell help. Here, we show how this divergence arises early in BCR signaling. Unlike sAg, pAg can bypass a Lyn-dependent negative feedback loop to trigger digital signaling, such that ultra-low concentrations of pAg produce strong and sustained Ca2+ responses. Surprisingly, pAg drives maximal nuclear NF-{kappa}B but limited NFAT, whereas sAg does the opposite, reflecting differential production of diacylglycerol. Consequently, sAg induced an NFAT-dependent anergy program, whereas pAg evaded this state and instead engaged a cMyc-driven program that partially resembles a TLR-dependent danger response. Our findings reveal how proximal signaling directs distinct transcriptional fate to enable immunogenic B cell responses to virus-like antigen display.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells 97%
- APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence 97%
- LAG-3 blockade reactivates the CD8+ T cell expansion program to re-expand contracted clones in the tumor 96%
Similar papers in this journal
- 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 98%
- SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 T cells 97%
- Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis 97%
Similar papers in this journal
Similar papers in this journal
"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.