%0 Journal Article
%T The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers
%A Benedetta Pozzi
%A Stefania Amodio
%A Caterina Lucano
%A Anna Sciullo
%A Simona Ronzoni
%A Daniela Castelletti
%A Thure Adler
%A Irina Treise
%A Ingrid Holmberg Betsholtz
%A Birgit Rathkolb
%A Dirk H. Busch
%A Eckhard Wolf
%A Helmut Fuchs
%A Val¨¦rie Gailus-Durner
%A Martin Hrab¨§ de Angelis
%A Christer Betsholtz
%A Stefano Casola
%A Pier Paolo Di Fiore
%A Nina Offenh£¿user
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0050818
%X 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0050818