LSD1 Cooperates with Noncanonical NF-κB Signaling to Regulate Marginal Zone B Cell Development

Haines, Robert R.; Scharer, Christopher D.; Lobby, Jenna L; Boss, Jeremy M.

doi:10.4049/jimmunol.1900654

Cited by 15 publications

(16 citation statements)

References 90 publications

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“…All chemical inhibitors were purchased from Sigma Aldrich (St. Louis, MO, USA). BMS345541, IKK16, and IMD0354 are specific inhibitors of IkB kinase (IKK) while Takinib is a specific inhibitor of TAK1 ( Figure 1 and Figure 2 ) [ 25 , 26 , 27 , 28 , 29 ]. Working stocks of 5 mg/mL were made in dimethyl sulfoxide (DMSO) for all inhibitors except for Takinib, which was dissolved at 2 mg/mL due to its lower solubility.…”

Section: Methodsmentioning

confidence: 99%

Effects of NF-kB Signaling Inhibitors on Bed Bug Resistance to Orally Provisioned Entomopathogenic Bacteria

Pietri¹,

Potts²

2021

Insects

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Bed bugs are globally important pests and there is an ongoing need for the development and improvement of bed bug control tools. Though promising against other insect pests, the exploration of biological methods for bed bug control is limited. Previously, we identified several species of bacteria that have entomopathogenic effects against bed bugs when ingested. We also described the conservation of several antibacterial responses in bed bugs, including the expression of immune effector genes regulated by NF-kB transcription factors through the Toll and immune deficiency (IMD) signaling pathways. Accordingly, we predicted that chemical inhibition of NF-kB signaling could reduce bed bug resistance to orally provisioned entomopathogenic bacteria, potentially improving their effectiveness as biological control agents. In the present study, we administered four small molecule inhibitors of NF-kB signaling (BMS345541, IKK16, IMD0354, Takinib) to bed bugs by feeding them in a blood meal. We then quantified basal mortality and mortality in response to oral infection with two different entomopathogenic bacteria (Pseudomonas entomophila and Bacillus thuringiensis israelensis). None of the NF-kB signaling inhibitors tested increased mortality above control levels when administered alone, suggesting a lack of direct toxicity. However, one inhibitor (IKK16) significantly enhanced the rate of mortality from oral infection with P. entomophila. Enhanced mortality was independent of direct effects of IKK16 on P. entomophila growth in vitro but was associated with higher bacterial loads in vivo (i.e., reduced resistance). Together, these results provide new insight into the regulation of the bed bug immune system and suggest that administration of entomopathogens in combination with inhibition of immune signaling pathways to reduce infection resistance may be effective for biological control of bed bugs.

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Section: Methodsmentioning

confidence: 99%

Effects of NF-kB Signaling Inhibitors on Bed Bug Resistance to Orally Provisioned Entomopathogenic Bacteria

Pietri¹,

Potts²

2021

Insects

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“…Conditional deletion of Lsd1 during B cell development resulted in a significant decrease in marginal zone B cells (MZB) but not on follicular B cells (FoB) 159 . MZB represent a small subset of splenic B cells that predominately respond to TI antigens 160,161 .…”

Section: Epigenetic Control Of Antibody‐secreting Cell Differentiationmentioning

confidence: 99%

“…Moreover, chromatin accessibility data indicated that NF‐κB like motifs were affected. Further analyses showed that the non‐canonical NF‐κB family member p52 interacted with LSD1, and that LSD1’s activity through the BAFF signaling pathways during transitional B cell development to MZB, was diminished in LSD1‐deficient cells 159 …”

Section: Epigenetic Control Of Antibody‐secreting Cell Differentiationmentioning

confidence: 99%

Epigenetic gene regulation in plasma cells

Patterson

Kania

Zuo

et al. 2021

Immunological Reviews

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Humoral immunity provides protection from pathogenic infection and is mediated by antibodies following the differentiation of naive B cells (nBs) to antibody‐secreting cells (ASCs). This process requires substantial epigenetic and transcriptional rewiring to ultimately repress the nB program and replace it with one conducive to ASC physiology and function. Notably, these reprogramming events occur within the framework of cell division. Efforts to understand the relationship of cell division with reprogramming and ASC differentiation in vivo have uncovered the timing and scope of reprogramming, as well as key factors that influence these events. Herein, we discuss the unique physiology of ASC and how nBs undergo epigenetic and genome architectural reorganization to acquire the necessary functions to support antibody production. We also discuss the stage‐wise manner in which reprogramming occurs across cell divisions and how key molecular determinants can influence B cell fate outcomes.

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“…In plasmacytoma cell lines, LSD1 interacts with BLIMP1 to remove H3K4me1 modifications and maintain repression on B cell lineage genes including CIITA , PAX5 , and SPIB 85 . After deletion of LSD1 at the late Pro‐B cell stage in the bone marrow, LSD1 deficiency leads to a reduction in marginal zone B cells but not follicular B cells 86 . This defect in marginal zone development was mediated through an interaction of LSD1 with the non‐canonical NF‐κB transcription factor p52, encoded by NFKB2 86 .…”

Section: Epigenetic Changes Instruct B Cell Differentiationmentioning

confidence: 99%

“…After deletion of LSD1 at the late Pro‐B cell stage in the bone marrow, LSD1 deficiency leads to a reduction in marginal zone B cells but not follicular B cells 86 . This defect in marginal zone development was mediated through an interaction of LSD1 with the non‐canonical NF‐κB transcription factor p52, encoded by NFKB2 86 . In TI‐I B cell responses, LSD1 is progressively upregulated, with expression peaking in ASC and in the absence of LSD1 there is a reduction in ASC and derepression of BLIMP1 target genes 24 .…”

Section: Epigenetic Changes Instruct B Cell Differentiationmentioning

confidence: 99%

Roadmap to a plasma cell: Epigenetic and transcriptional cues that guide B cell differentiation

Wiggins

Scharer

2020

Immunological Reviews

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B cell differentiation is a multistep process that ultimately leads to the formation of plasma cells or antibody-secreting cells (ASCs), a specialized cell type that functions as an antibody factory. Once initiated, B cell differentiation encompasses multiple transitory cell types that allow for amplification of responding cells and diversification of the antibody repertoire as well as cell fate endpoints such as antigen-experienced memory and short-and long-lived ASC. Aided by the adoption of genomic profiling techniques that are rapidly improving in sensitivity, it is now possible to profile the molecular changes that occur in rare transitory B cell differentiation stages and patient samples where cells are limiting. In this review, we will discuss how cell division influences the transcriptome, transcription factor networks, and epigenetic programs that are remodeled during B cell differentiation, and provide a generalized roadmap for ASC differentiation.

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LSD1 Cooperates with Noncanonical NF-κB Signaling to Regulate Marginal Zone B Cell Development

Abstract: This information is current as Development Signaling to Regulate Marginal Zone B Cell B κ LSD1 Cooperates with Noncanonical NFand Jeremy M. Boss

Cited by 15 publications

References 90 publications

Effects of NF-kB Signaling Inhibitors on Bed Bug Resistance to Orally Provisioned Entomopathogenic Bacteria

Effects of NF-kB Signaling Inhibitors on Bed Bug Resistance to Orally Provisioned Entomopathogenic Bacteria

Epigenetic gene regulation in plasma cells

Roadmap to a plasma cell: Epigenetic and transcriptional cues that guide B cell differentiation

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