SPARC deficiency affects bone marrow stromal function, resulting in impaired B lymphopoiesis

J Leukoc Biol. 2014 Jul;96(1):73-82. doi: 10.1189/jlb.1A0713-415RR. Epub 2014 Mar 5.


It has been demonstrated that B cells were decreased in the BM of SPARC-null mice, accompanied by a lack of immune response to LPS. However, the effect of SPARC deficiency on B lymphopoiesis remains unclear. Herein, we investigated the role of SPARC in the regulation of B lymphopoiesis, as well as the underlying molecular mechanisms. In present study, we found that the size of B-lineage progenitors (pro-B and pre-B plus immature B cells) and primitive hematopoietic cells (LSK and LTC cells) were reduced, whereas multipotent progenitors (CFU-S12) were increased in BM of SPARC-null mice. When SPARC-null BM cells were transplanted into lethally irradiated WT mice, the B cell population in recipients was restored to a level equivalent to that generated by WT BM cells, suggesting that the changes of the BM microenvironment in SPARC-null mice affect B lymphopoiesis. Furthermore, we found that SPARC-null BMSCs did not support the differentiation of WT BM cells into the B cell population in vitro, and conditioned medium derived from SPARC-null BMSCs inhibited B cell differentiation. However, the addition of rmSPARC to the coculture system did not restore the impaired B lymphopoiesis. In summary, our findings suggest that SPARC plays a crucial role in the regulation of early B lymphopoiesis.

Keywords: B cell progenitors; BM stromal cells; primitive hematopoietic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Cellular Microenvironment / physiology*
  • Coculture Techniques
  • Lymphopoiesis / physiology*
  • Mice
  • Mice, Mutant Strains
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • Osteonectin / genetics
  • Osteonectin / metabolism*
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / metabolism*
  • Stromal Cells / cytology
  • Stromal Cells / metabolism


  • Osteonectin
  • SPARC protein, mouse