title: The autophagy gene ATG5 plays an essential role in B lymphocyte development.
abstract: Macroautophagy (herein autophagy) is an evolutionarily conserved process, requiring the gene ATG5, by which cells degrade cytoplasmic constituents and organelles. Here we show that ATG5 is required for efficient B cell development and for the maintenance of B-1a B cell numbers. Deletion of ATG5 in B lymphocytes using Cre-LoxP technology or repopulation of irradiated mice with ATG5-/- fetal liver progenitors resulted in a dramatic reduction in B-1 B cells in the peritoneum. ATG5-/- progenitors exhibited a significant defect in B cell development at the pro- to pre-B cell transition, although a proportion of pre-B cells survived to populate the periphery. Inefficient B cell development in the bone marrow was associated with increased cell death, indicating that ATG5 is important for B cell survival during development. In addition, B-1a B cells require ATG5 for their maintenance in the periphery. We conclude that ATG5 is differentially required at discrete stages of development in distinct, but closely related, cell lineages.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Miller
authors.forename: Zijiang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Linda M
authors.initials: LM
authors.lastname: Stephenson
authors.forename: Ken
authors.initials: K
authors.lastname: Cadwell
authors.forename: Heather H
authors.initials: HH
authors.lastname: Pua
authors.forename: Heung Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Noboru N
authors.initials: NN
authors.lastname: Mizushima
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
authors.forename: Wojciech
authors.initials: W
authors.lastname: Swat
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D019070:Cell Lineage; D002470:Cell Survival; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins