The autophagy gene ATG5 plays an essential role in B lymphocyte development.
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.
Miller
Brian C
BC
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Zhao
Zijiang
Z
Stephenson
Linda M
LM
Cadwell
Ken
K
Pua
Heather H
HH
Lee
Heung Kyu
HK
Mizushima
Noboru N
NN
Iwasaki
Akiko
A
He
You-Wen
YW
Swat
Wojciech
W
Virgin
Herbert W
HW
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
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins