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Updated: Apr 11, 2026

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
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FNIP1 Modulates B Cell Receptor Signaling Strength by Coordinating Metabolism During Development.

Heon Park1, Ryan Culbert1, Dechen Sakya1

  • 1Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.

Biorxiv : the Preprint Server for Biology
|April 10, 2026
PubMed
Summary

Folliculin Interacting Protein 1 (Fnip1) is crucial for transitional B cell development and peripheral tolerance. Loss of Fnip1 arrests B cell maturation, impacting immune homeostasis.

Keywords:
CD19Cell survivalNegative selectionPeripheral toleranceRagDTFEBTransitional B cells

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Area of Science:

  • Immunology
  • Cell Biology
  • Metabolism

Background:

  • B cell development requires checkpoints to ensure immune competence and prevent autoimmunity.
  • Transitional B cells differentiate into follicular (FO) and marginal zone (MZ) B cells, regulated by B cell receptor (BCR) signaling, metabolism, and survival signals.

Purpose of the Study:

  • To identify key regulators of transitional B cell development and differentiation.
  • To elucidate the role of Folliculin Interacting Protein 1 (Fnip1) in B cell fate decisions and immune homeostasis.

Main Methods:

  • Utilized conditional Fnip1-deficient mice (Fnip1 fl/fl CD21Cre).
  • Analyzed B cell populations using flow cytometry (B220, CD93, CD19).
  • Investigated signaling pathways including AMPK/FLCN/TFEB and CD19/PI3K/Akt/mTORC1.
  • Employed the MD4/mHEL/sHEL tolerance model.

Main Results:

  • Loss of Fnip1 caused developmental arrest at the transitional B220⁺CD93mid stage.
  • Fnip1 deficiency severely impaired FO and MZ B cell differentiation, leading to accumulation of CD19high, RAG-negative B cells.
  • Fnip1 regulates BCR signaling thresholds and metabolic programming by controlling TFEB nuclear localization.
  • Fnip1 is essential for maintaining peripheral tolerance, though dispensable for negative selection.

Conclusions:

  • Fnip1 acts as a metabolic gatekeeper, integrating nutrient sensing with BCR signaling to control transitional B cell fate.
  • Fnip1 plays a critical role in maintaining immune homeostasis and peripheral tolerance.
  • Targeting Fnip1 may offer therapeutic strategies for immune regulation.