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

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.

SUBMITTER: Park H

PROVIDER: S-EPMC3361584 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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

Park Heon H Staehling Karen K Tsang Mark M Appleby Mark W MW Brunkow Mary E ME Margineantu Daciana D Hockenbery David M DM Habib Tania T Liggitt H Denny HD Carlson George G Iritani Brian M BM

Immunity 20120517 5

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 ...[more]

PMID: 22608497

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

Publications

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

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