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Updated: Oct 8, 2025

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Conditional deletion of mTOR discloses its essential role in early B-cell development

Shuling Zhang1, Wendy Dubois1, Xingmin Feng2

  • 1Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Molecular Carcinogenesis
|December 29, 2021
PubMed

Insights

Mechanistic target of rapamycin (mTOR) is crucial for early B-cell development. Disrupting mTOR in mice blocks B-cell maturation, impairing immune responses and antibody production.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Mechanistic target of rapamycin (mTOR) regulates cell growth, differentiation, and survival.
  • mTOR is frequently hyperactivated in cancers and plays a role in immune cell function.
  • The role of mTOR in early B-cell development remains largely unexplored.

Purpose of the Study:

  • To investigate the essential role of mTOR in early B-cell development and survival.
  • To elucidate the impact of mTOR disruption on B-cell maturation and immune responses.

Main Methods:

  • Conditional disruption of mTOR in developing mouse B cells.
  • Analysis of B-cell proliferation, survival, and developmental stages.
  • Immunization studies with NP-CGG antigen.
  • Competitive bone marrow (BM) repopulation assays.

Main Results:

  • Conditional disruption of mTOR led to reduced pre-B-cell proliferation and survival.
  • A developmental block at the pre-B-cell stage was observed, resulting in a lack of peripheral B cells.
  • Mice with disrupted mTOR showed impaired germinal center formation and antibody production upon immunization.
  • Conditional knockout BM cells were unable to reconstitute B cells in competitive repopulation assays.

Conclusions:

  • mTOR is essential for early pre-B-cell development and survival.
  • Disruption of mTOR significantly impacts B-cell maturation and the adaptive immune response.
  • Targeting mTOR may have implications for treating B-cell malignancies and immune disorders.
Keywords:
B-cell developmentMb1-Cre miceantibody productioncompetitive BM transplantationmTOR

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