The autophagy gene ATG5 plays an essential role in B lymphocyte development.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Miller, BC; Zhao, Z; Stephenson, LM; Cadwell, K; Pua, HH; Lee, HK; Mizushima, NN; Iwasaki, A; He, Y-W; Swat, W; Virgin, HW

Published Date

  • April 2008

Published In

Volume / Issue

  • 4 / 3

Start / End Page

  • 309 - 314

PubMed ID

  • 18188005

Pubmed Central ID

  • 18188005

Electronic International Standard Serial Number (EISSN)

  • 1554-8635

Digital Object Identifier (DOI)

  • 10.4161/auto.5474

Language

  • eng

Conference Location

  • United States