FNIP1 Modulates B Cell Receptor Signaling Strength by Coordinating Metabolism During Development
, RAG negative B cells. Fnip1 modulates BCR signaling thresholds and metabolic programming by regulating the AMPK/FLCN/TFEB and CD19/PI3K/Akt/mTORC1 pathways through restricting TFEB access to the nucleus. Using the MD4/mHEL/sHEL tolerance model, we show that Fnip1 is dispensable for negative selection but is essential for maintaining peripheral tolerance. Together, our findings define Fnip1 as a metabolic gatekeeper that integrates nutrient-sensing pathways with BCR signaling to orchestrate transitional B cell fate decisions, promote peripheral tolerance, and maintain immune homeostasis.
Authors
- Ryan Z Culbert
- Heon J. Park
- Brian M. Iritani (ORCID: https://orcid.org/0000-0003-1903-7850)
- Raynah Silprasert
- Dechen Sakya
Institutions
- University of Washington (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-01
- DOI
- https://doi.org/10.64898/2026.03.30.715168
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Washington
- National Institutes of Health