The special unfolded protein response in plasma cells

Ricci, Daniela; Gidalevitz, Tali; Argon, Yair

doi:10.1111/imr.13012

Cited by 16 publications

(20 citation statements)

References 181 publications

(280 reference statements)

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“…During B cell differentiation, the anticipatory events are not directly dependent on the splicing of the mammalian bZIP60 ortholog, XBP1 ( Gass et al, 2002 ; Ricci et al, 2021 ). It has been hypothesized that XBP1 could be activated by cell differentiation per se or to become “hypersensitive,” before its full activation due to high IgM synthesis ( van Anken et al, 2021 ).…”

Section: Challenges and Perspectivesmentioning

confidence: 99%

StresSeed: The Unfolded Protein Response During Seed Development

Vitale

2022

Front. Plant Sci.

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During seed development, the endoplasmic reticulum (ER) takes care of the synthesis and structural maturation of very high amounts of storage proteins in a relatively short time. The ER must thus adjust its extension and machinery to optimize this process. The major signaling mechanism to maintain ER homeostasis is the unfolded protein response (UPR). Both storage proteins that assemble into ER-connected protein bodies and those that are delivered to protein storage vacuoles stimulate the UPR, but its extent and features are specific for the different storage protein classes and even for individual members of each class. Furthermore, evidence exists for anticipatory UPR directly connected to the development of storage seed cells and for selective degradation of certain storage proteins soon after their synthesis, whose signaling details are however still largely unknown. All these events are discussed, also in the light of known features of mammalian UPR.

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Section: Challenges and Perspectivesmentioning

confidence: 99%

StresSeed: The Unfolded Protein Response During Seed Development

Vitale

2022

Front. Plant Sci.

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“…7a ). ER stress regulates the capacity of plasma cells to produce immunoglobulins 48 , likely because large quantities of misfolded antibodies 49 must be degraded, generating significant lysine 50 .…”

Section: Resultsmentioning

confidence: 99%

Supervised discovery of interpretable gene programs from single-cell data

Kunes

Walle

Nawy

et al. 2022

Preprint

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Factor analysis can drive biological discovery by decomposing single-cell gene expression data into a minimal set of gene programs that correspond to processes executed by cells in a sample. However, matrix factorization methods are prone to technical artifacts and poor factor interpretability. We have developed Spectra, an algorithm that identifies user-provided gene programs, modifies them to dataset context as needed, and detects novel programs that together best explain expression covariation. Spectra overcomes the dominance of cell-type signals by modeling cell-type-specific programs, and can characterize interpretable cell states along a continuum. We show that it outperforms existing approaches in challenging tumor immune contexts; Spectra finds factors that change under immune checkpoint therapy, disentangles the highly correlated features of CD8+ T-cell tumor reactivity and exhaustion, finds a novel program that explains continuous macrophage state changes under therapy, and identifies cell-type-specific immune metabolic programs.

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“…ZBP1 likely performs similar roles in some non-lymphoid tissues ( Figure 1 C). In melanocytes, ZBP1 is potentially activated by the DNA damaging effects of sunlight and skin-penetrant environmental mutagens to induce either RCD or ICD [ 42 , 43 ]. ZBP1 may play a role as a genetic modifier in some human mendelian diseases.…”

Section: Zbp1 and Mendelian Diseasementioning

confidence: 99%

“…They have a unique biology related to their high levels of immunoglobulin production. Their survival depends on the unfolded protein response (UPR) to minimize the stresses associated with protein aggregation and antibody secretion [ 42 ]. With their optimized protein production line, PCs are an ideal factory for viruses to replicate themselves in.…”

Section: Plasma Cells As Factories For Viral Productionmentioning

confidence: 99%

“…These TF include POU2AF1 [ 56 ], TNFRSF17 (also called B-cell maturation antigen (BCMA)), XBP1, ATF4, KLF13 and MEF2B [ 45 , 52 ] that are coexpressed with ZBP1 ( Figure 4 A–C). The transcription factors XBP1, PDRM1 and IRF4 are also components of the UPR that is regulated by the heat shock protein HSPA5 [ 42 ] and facilitate the packaging of EBV replicons.…”

Section: Plasma Cells As Factories For Viral Productionmentioning

confidence: 99%

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Mono a Mano: ZBP1’s Love–Hate Relationship with the Kissing Virus

Herbert

Федоров

Poptsova

2022

IJMS

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Z-DNA binding protein (ZBP1) very much represents the nuclear option. By initiating inflammatory cell death (ICD), ZBP1 activates host defenses to destroy infectious threats. ZBP1 is also able to induce noninflammatory regulated cell death via apoptosis (RCD). ZBP1 senses the presence of left-handed Z-DNA and Z-RNA (ZNA), including that formed by expression of endogenous retroelements. Viruses such as the Epstein–Barr “kissing virus” inhibit ICD, RCD and other cell death signaling pathways to produce persistent infection. EBV undergoes lytic replication in plasma cells, which maintain detectable levels of basal ZBP1 expression, leading us to suggest a new role for ZBP1 in maintaining EBV latency, one of benefit for both host and virus. We provide an overview of the pathways that are involved in establishing latent infection, including those regulated by MYC and NF-κB. We describe and provide a synthesis of the evidence supporting a role for ZNA in these pathways, highlighting the positive and negative selection of ZNA forming sequences in the EBV genome that underscores the coadaptation of host and virus. Instead of a fight to the death, a state of détente now exists where persistent infection by the virus is tolerated by the host, while disease outcomes such as death, autoimmunity and cancer are minimized. Based on these new insights, we propose actionable therapeutic approaches to unhost EBV.

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The special unfolded protein response in plasma cells

Cited by 16 publications

References 181 publications

StresSeed: The Unfolded Protein Response During Seed Development

StresSeed: The Unfolded Protein Response During Seed Development

Supervised discovery of interpretable gene programs from single-cell data

Mono a Mano: ZBP1’s Love–Hate Relationship with the Kissing Virus

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