The endocytic adaptor Eps15 controls marginal zone B cell numbers

PLoS One. 2012;7(11):e50818. doi: 10.1371/journal.pone.0050818. Epub 2012 Nov 30.


Eps15 is an endocytic adaptor protein involved in clathrin and non-clathrin mediated endocytosis. In Caenorhabditis elegans and Drosophila melanogaster lack of Eps15 leads to defects in synaptic vesicle recycling and synapse formation. We generated Eps15-KO mice to investigate its function in mammals. Eps15-KO mice are born at the expected Mendelian ratio and are fertile. Using a large-scale phenotype screen covering more than 300 parameters correlated to human disease, we found that Eps15-KO mice did not show any sign of disease or neural deficits. Instead, altered blood parameters pointed to an immunological defect. By competitive bone marrow transplantation we demonstrated that Eps15-KO hematopoietic precursor cells were more efficient than the WT counterparts in repopulating B220⁺ bone marrow cells, CD19⁻ thymocytes and splenic marginal zone (MZ) B cells. Eps15-KO mice showed a 2-fold increase in MZ B cell numbers when compared with controls. Using reverse bone marrow transplantation, we found that Eps15 regulates MZ B cell numbers in a cell autonomous manner. FACS analysis showed that although MZ B cells were increased in Eps15-KO mice, transitional and pre-MZ B cell numbers were unaffected. The increase in MZ B cell numbers in Eps15 KO mice was not dependent on altered BCR signaling or Notch activity. In conclusion, in mammals, the endocytic adaptor protein Eps15 is a regulator of B-cell lymphopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Bone Marrow Transplantation
  • Cell Count*
  • Endocytosis*
  • Female
  • Gene Knockout Techniques
  • Male
  • Mice
  • Receptors, Notch / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology


  • Adaptor Proteins, Signal Transducing
  • Eps15 protein, mouse
  • Receptors, Notch

Grants and funding

This work was funded by grants from AIRC (Associazione Italiana per la Ricerca sul Cancro), Fondazione Monzino and Fondazione Ferrari to PPDF, and by grants from the German Federal Ministry of Education and Research, NGFN-Plus grant numbers 01GS0850 to MHdA, 01GS0851 to EW and 01GS0852 to DB. The German Mouse clinic received funding from Infrafrontier (01KX1012 and 211404) and the European Union (EUMODIC LSHG-2006–037188). SC is supported by the Italian Foundation for Cancer Research (FIRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.