Endoplasmic reticulum-resident E3 ubiquitin ligase Hrd1 controls B-cell immunity through degradation of the death receptor CD95/Fas. Conference Paper uri icon


  • Humoral immunity involves multiple checkpoints during B-cell development, maturation, and activation. The cell death receptor CD95/Fas-mediated apoptosis plays a critical role in eliminating the unwanted activation of B cells by self-reactive antigens and in maintaining B-cell homeostasis through activation-induced B-cell death (AICD). The molecular mechanisms controlling AICD remain largely undefined. Herein, we show that the E3 ubiquitin ligase Hrd1 protected B cells from activation-induced cell death by degrading the death receptor Fas. Hrd1-null B cells exhibited high Fas expression during activation and rapidly underwent Fas-mediated apoptosis, which could be largely inhibited by FasL neutralization. Fas mutation in Hrd1 KO mice abrogated the increase in B-cell AICD. We identified Hrd1 as the first E3 ubiquitin ligase of the death receptor Fas and Hrd1-mediated Fas destruction as a molecular mechanism in regulating B-cell immunity.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 0.5

author list (cited authors)

  • Kong, S., Yang, Y. i., Xu, Y., Wang, Y., Zhang, Y., Melo-Cardenas, J., ... Fang, D.

citation count

  • 25

complete list of authors

  • Kong, Sinyi||Yang, Yi||Xu, Yuanming||Wang, Yajun||Zhang, Yusi||Melo-Cardenas, Johanna||Xu, Xiangping||Gao, Beixue||Thorp, Edward B||Zhang, Donna D||Zhang, Bin||Song, Jianxun||Zhang, Kezhong||Zhang, Jianning||Zhang, Jinping||Li, Huabin||Fang, Deyu

publication date

  • September 2016