BCR-mediated apoptosis associated with negative selection of immature B cells is selectively dependent on Pten Academic Article uri icon

Overview

MeSH Major

  • Apoptosis
  • PTEN Phosphohydrolase
  • Precursor Cells, B-Lymphoid
  • Receptors, Antigen, B-Cell

abstract

  • The molecular basis of B cell receptor (BCR)-induced apoptosis during the negative selection of immature B cells is largely unknown. We use transitional immature B cells that are highly susceptible to BCR-induced apoptosis to show that Pten is selectively required for BCR-mediated initiation of the mitochondrial death pathway. Specifically, deleting Pten, but not other pro-apoptotic molecules, abrogates BCR-elicited apoptosis and improves viability in wild-type immature B cells. We further identify a physiologically and significantly higher intracellular Pten level in immature B cells, as compared to mature B cells, which is responsible for low AKT activity and the propensity towards death in immature B cells. Restoration of AKT activity using a constitutive form of AKT or reduction of Pten to a level comparable with that seen in mature B cells rescues immature B cells from BCR-induced apoptosis. Thus, we provide evidence that Pten is an essential mediator of BCR-induced cell death, and that differential regulation of intracellular Pten levels determines whether BCR ligation promotes cell death or survival. Our findings provide a valuable insight into the mechanisms underlying negative selection and clonal deletion of immature B cells.

publication date

  • February 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/cr.2008.284

PubMed ID

  • 18781138

Additional Document Info

start page

  • 196

end page

  • 207

volume

  • 19

number

  • 2