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

Publication ,  Journal Article
Poe, JC; Kountikov, EI; Lykken, JM; Natarajan, A; Marchuk, DA; Tedder, TF
Published in: J Exp Med
January 13, 2014

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.

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Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

January 13, 2014

Volume

211

Issue

1

Start / End Page

57 / 69

Location

United States

Related Subject Headings

  • Uridylate-Specific Endoribonucleases
  • Signal Transduction
  • Sialic Acid Binding Ig-like Lectin 2
  • Self Tolerance
  • Quantitative Trait Loci
  • Proto-Oncogene Proteins c-myc
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology
 

Citation

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Poe, J. C., Kountikov, E. I., Lykken, J. M., Natarajan, A., Marchuk, D. A., & Tedder, T. F. (2014). EndoU is a novel regulator of AICD during peripheral B cell selection. J Exp Med, 211(1), 57–69. https://doi.org/10.1084/jem.20130648
Poe, Jonathan C., Evgueni I. Kountikov, Jacquelyn M. Lykken, Abirami Natarajan, Douglas A. Marchuk, and Thomas F. Tedder. “EndoU is a novel regulator of AICD during peripheral B cell selection.J Exp Med 211, no. 1 (January 13, 2014): 57–69. https://doi.org/10.1084/jem.20130648.
Poe JC, Kountikov EI, Lykken JM, Natarajan A, Marchuk DA, Tedder TF. EndoU is a novel regulator of AICD during peripheral B cell selection. J Exp Med. 2014 Jan 13;211(1):57–69.
Poe, Jonathan C., et al. “EndoU is a novel regulator of AICD during peripheral B cell selection.J Exp Med, vol. 211, no. 1, Jan. 2014, pp. 57–69. Pubmed, doi:10.1084/jem.20130648.
Poe JC, Kountikov EI, Lykken JM, Natarajan A, Marchuk DA, Tedder TF. EndoU is a novel regulator of AICD during peripheral B cell selection. J Exp Med. 2014 Jan 13;211(1):57–69.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

January 13, 2014

Volume

211

Issue

1

Start / End Page

57 / 69

Location

United States

Related Subject Headings

  • Uridylate-Specific Endoribonucleases
  • Signal Transduction
  • Sialic Acid Binding Ig-like Lectin 2
  • Self Tolerance
  • Quantitative Trait Loci
  • Proto-Oncogene Proteins c-myc
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology