Molecular Evaluation of Endoplasmic Reticulum Homeostasis Meets Humoral Immunity

Eelco van Anken, Anush Bakunts, Chih Chi Andrew Hu, Sophie Janssens, Roberto Sitia

Research output: Contribution to journalReview article


The biosynthesis of about one third of the human proteome, including membrane receptors and secreted proteins, occurs in the endoplasmic reticulum (ER). Conditions that perturb ER homeostasis activate the unfolded protein response (UPR). An ‘optimistic’ UPR output aims at restoring homeostasis by reinforcement of machineries that guarantee efficiency and fidelity of protein biogenesis in the ER. Yet, once the UPR ‘deems’ that ER homeostatic readjustment fails, it transitions to a ‘pessimistic’ output, which, depending on the cell type, will result in apoptosis. In this article, we discuss emerging concepts on how the UPR ‘evaluates’ ER stress, how the UPR is repurposed, in particular in B cells, and how UPR-driven counter-selection of cells undergoing homeostatic failure serves organismal homeostasis and humoral immunity.

Original languageEnglish (US)
JournalTrends in Cell Biology
StateAccepted/In press - 2021


  • antibody production
  • B cell development
  • endoplasmic reticulum
  • proteostasis
  • RIDD
  • unfolded protein response

ASJC Scopus subject areas

  • Cell Biology

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