B-cell homeostasis: digital survival or analog growth?

Journal Article (Journal Article;Review)

Maintenance of B-lymphocyte homeostasis requires balanced cell production, death, and proliferation. To coordinate these processes, B cells are dependent on cell extrinsic signals. In lymphocyte development, precursor cells are dependent on Fms-like tyrosine kinase ligand 3 (Flt3L), and pre-B cells are dependent on the cytokine interleukin-7. Transitional B cells require B-lymphocyte stimulator (BLyS) for survival. Mature B cells require B-cell receptor (BCR) signals and also remain sensitive to their microenvironment. An emerging model suggests that extrinsic signals do not regulate B-cell survival through a digital mechanism where cells are simply instructed to survive or die. Instead, availability and competition for extrinsic signals regulates cellular physiology and metabolism in an analog fashion that then influences cell commitment to apoptosis or proliferation. Decreases in cellular metabolism may sensitize cells to activation and action of the pro-apoptotic Bcl-2 family members, Bak and Bax, and promote apoptosis. In contrast, increases in metabolism may predispose cells to proliferate. Analog control of cell physiology can, thus, be integrated with other inputs by individual cells to produce a fate decision for survival, proliferation, or apoptosis and prevent diseases of cell death, such as immunodeficiency, and cell activation and proliferation, such as autoimmunity or cancer.

Full Text

Duke Authors

Cited Authors

  • Rathmell, JC

Published Date

  • February 2004

Published In

Volume / Issue

  • 197 /

Start / End Page

  • 116 - 128

PubMed ID

  • 14962191

International Standard Serial Number (ISSN)

  • 0105-2896

Digital Object Identifier (DOI)

  • 10.1111/j.0105-2896.2004.0096.x


  • eng

Conference Location

  • England