title: Eukaryotic initiation factor 2alpha phosphorylation is required for B-cell maturation and function in mice.
abstract: BACKGROUND
  The control of translation initiation is a crucial component in the regulation of gene expression. The eukaryotic initiation factor 2α (eIF2α) mediates binding of the initiator transfer-messenger-RNA to the AUG initiation codon, and thus controls a rate-limiting step in translation initiation. Phosphorylation of eIF2α at serine 51 is linked to cellular stress response and attenuates translation initiation. The biochemistry of translation inhibition mediated by eIF2α phosphorylation is well characterized, yet the physiological importance in hematopoiesis remains only partially known.
  
  
  METHODS
  Using hematopoietic stem cells carrying a non-phosphorylatable mutant form of eIF2α (eIF2αAA), we examined the efficiency of reconstitution in wild-type and B-cell-deficient microMT C57BL/6 recipients in two independent models.
  
  
  RESULTS
  We provide evidence that phosphorylation-deficient eIF2α mutant hematopoietic stem cells may repopulate lethally irradiated mice but have a defect in the development and maintenance of newly formed B cells in the bone marrow and of naïve follicular B cells in the periphery. The mature B-cell compartment is markedly reduced in bone marrow, spleen and peripheral blood, and B-cell receptor-mediated proliferation in vitro and serum immunoglobulin secretion in vivo are impaired.
  
  
  CONCLUSIONS
  The data suggest that regulation of translation through eIF2α phosphorylation is dispensable in hematopoietic reconstitution but essential during late B-cell development.
authors.affiliation: Department of Hematology and Oncology, Charité, Campus Virchow-Klinikum, University Medicine Berlin, Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Mielke
authors.forename: Rolf
authors.initials: R
authors.lastname: Schwarzer
authors.forename: Cornelis F
authors.initials: CF
authors.lastname: Calkhoven
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Kaufman
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Achim
authors.initials: A
authors.lastname: Leutz
authors.forename: Franziska
authors.initials: F
authors.lastname: Jundt
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002678:Chimera; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D013234:Stem Cells / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D015852:Eukaryotic Initiation Factor-2