EndoU is a novel regulator of AICD during peripheral B cell selection.

Journal Article

Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22(-/-[B6])) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag-specific B cells in Ig(Tg) hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance.

Full Text

Duke Authors

Cited Authors

  • Poe, JC; Kountikov, EI; Lykken, JM; Natarajan, A; Marchuk, DA; Tedder, TF

Published Date

  • January 13, 2014

Published In

Volume / Issue

  • 211 / 1

Start / End Page

  • 57 - 69

PubMed ID

  • 24344237

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20130648

Language

  • eng

Conference Location

  • United States