mTORC1 plays an important role in osteoblastic regulation of B-lymphopoiesis

Sci Rep. 2018 Sep 28;8(1):14501. doi: 10.1038/s41598-018-32858-5.


Skeletal osteoblasts are important regulators of B-lymphopoiesis, serving as a rich source of factors such as CXCL12 and IL-7 which are crucial for B-cell development. Recent studies from our laboratory and others have shown that deletion of Rptor, a unique component of the mTORC1 nutrient-sensing complex, early in the osteoblast lineage development results in defective bone development in mice. In this study, we now demonstrate that mTORC1 signalling in pre-osteoblasts is required for normal B-lymphocyte development in mice. Targeted deletion of Rptor in osterix-expressing pre-osteoblasts (Rptorob-/-) leads to a significant reduction in the number of B-cells in the bone marrow, peripheral blood and spleen at 4 and 12 weeks of age. Rptorob-/- mice also exhibit a significant reduction in pre-B and immature B-cells in the BM, indicative of a block in B-cell development from the pro-B to pre-B cell stage. Circulating levels of IL-7 and CXCL12 are also significantly reduced in Rptorob-/- mice. Importantly, whilst Rptor-deficient osteoblasts are unable to support HSC differentiation to B-cells in co-culture, this can be rescued by the addition of exogenous IL-7 and CXCL12. Collectively, these findings demonstrate that mTORC1 plays an important role in extrinsic osteoblastic regulation of B-cell development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism
  • Chemokine CXCL12 / biosynthesis
  • Chemokine CXCL12 / blood
  • Chemokine CXCL12 / pharmacology
  • Coculture Techniques
  • Down-Regulation
  • Genes, Reporter
  • Interleukin-7 / blood
  • Interleukin-7 / pharmacology
  • Lymphopoiesis / physiology*
  • Mechanistic Target of Rapamycin Complex 1 / physiology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Osteoblasts / metabolism*
  • RNA, Messenger / biosynthesis
  • Regulatory-Associated Protein of mTOR / deficiency
  • Regulatory-Associated Protein of mTOR / genetics
  • Regulatory-Associated Protein of mTOR / physiology
  • Sp7 Transcription Factor / metabolism


  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Interleukin-7
  • RNA, Messenger
  • Regulatory-Associated Protein of mTOR
  • Rptor protein, mouse
  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • interleukin-7, mouse
  • Mechanistic Target of Rapamycin Complex 1