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Research Paper
The autophagy gene ATG5 plays an essential role in B lymphocyte development
Brian C. Miller, Zijiang Zhao, Linda M. Stephenson, Ken Cadwell, Heather H. Pua, Heung Kyu Lee, Noboru Mizushima, Akiko Iwasaki, You-Wen He, Wojciech Swat and Herbert W. Virgin
volume 4 | issue 3
1 April 2008Pages: 309 - 314
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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
Brian C. Miller
Washington University School of Medicine
Zijiang Zhao
Washington University School of Medicine
Linda M. Stephenson
Washington University in St. Louis
Ken Cadwell
Washington University in St. Louis
Heather H. Pua
Duke University Medical Center
Heung Kyu Lee
Yale University School of Medicine
Noboru Mizushima
Tokyo Medical and Dental University
Akiko Iwasaki
Yale University School of Medicine
You-Wen He
Duke University Medical Center
Wojciech Swat
Washington University School of Medicine
Herbert W. Virgin
Washington University School of Medicine