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Immunity. 2012 May 25;36(5):769-81. doi: 10.1016/j.immuni.2012.02.019. Epub 2012 May 17.

Disruption of Fnip1 reveals a metabolic checkpoint controlling B lymphocyte development.

Author information

1
The Department of Comparative Medicine, University of Washington, Seattle, WA 98195-7190, USA.

Abstract

The coordination of nutrient and energy availability with cell growth and division is essential for proper immune cell development and function. By using a chemical mutagenesis strategy in mice, we identified a pedigree that has a complete block in B cell development at the pre-B cell stage resulting from a deletion in the Fnip1 gene. Enforced expression of an immunoglobulin transgene failed to rescue B cell development. Whereas essential pre-B cell signaling molecules were activated normally in Fnip1-null pre-B cells, the metabolic regulators AMPK and mTOR were dysregulated, resulting in excessive cell growth and enhanced sensitivity to apoptosis in response to metabolic stress (pre-B cell receptor crosslinking, oncogene activation). These results indicate that Folliculin-interacting protein 1 (Fnip1) is vital for B cell development and metabolic homeostasis and reveal a metabolic checkpoint that may ensure that pre-B cells have sufficient metabolic capacity to support division, while limiting lymphomagenesis caused by deregulated growth.

PMID:
22608497
PMCID:
PMC3361584
DOI:
10.1016/j.immuni.2012.02.019
[Indexed for MEDLINE]
Free PMC Article

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