title: The endocytic adaptor Eps15 controls marginal zone B cell numbers.
abstract: 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.
authors.affiliation: IFOM Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Pozzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Amodio
authors.forename: Caterina
authors.initials: C
authors.lastname: Lucano
authors.forename: Anna
authors.initials: A
authors.lastname: Sciullo
authors.forename: Simona
authors.initials: S
authors.lastname: Ronzoni
authors.forename: Daniela
authors.initials: D
authors.lastname: Castelletti
authors.forename: Thure
authors.initials: T
authors.lastname: Adler
authors.forename: Irina
authors.initials: I
authors.lastname: Treise
authors.forename: Ingrid Holmberg
authors.initials: IH
authors.lastname: Betsholtz
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.forename: Valérie
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: Martin Hrabě
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.forename: Stefano
authors.initials: S
authors.lastname: Casola
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
authors.forename: Nina
authors.initials: N
authors.lastname: Offenhäuser
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D016026:Bone Marrow Transplantation; D002452:Cell Count; D004705:Endocytosis; D005260:Female; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D051880:Receptors, Notch / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C082729:Eps15 protein, mouse; D051880:Receptors, Notch