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, Herbert W. Virgin IV

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230 Scopus citations

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.

Original languageEnglish
Pages (from-to)309-314
Number of pages6
JournalAutophagy
Volume4
Issue number3
DOIs
StatePublished - Apr 1 2008

Keywords

  • ATG5
  • B cells
  • Cell differentiation and development
  • Transgenic/knockout mice

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    Miller, B. C., Zhao, Z., Stephenson, L. M., Cadwell, K., Pua, H. H., Lee, H. K., Mizushima, N., Iwasaki, A., He, Y. W., Swat, W., & Virgin IV, H. W. (2008). The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy, 4(3), 309-314. https://doi.org/10.4161/auto.5474