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.

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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

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article

FNIP1 Modulates B Cell Receptor Signaling Strength by Coordinating Metabolism During Development

Ryan Z Culbert, Heon J. Park, Brian M. Iritani, Raynah Silprasert et al.
bioRxiv (Cold Spring Harbor Laboratory)
T-cell and B-cell Immunology
article

FNIP1 Modulates B Cell Receptor Signaling Strength by Coordinating Metabolism During Development

Ryan Z Culbert, Heon J. Park, Brian M. Iritani, Raynah Silprasert, Dechen Sakya
article en

Abstract

, 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.

bioRxiv (Cold Spring Harbor Laboratory)
University of Washington (US)
University of Washington, National Institutes of Health
Openalex Percentile: Top 29%
T-cell and B-cell Immunology
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