Efficient B Cell Depletion via Diphtheria Toxin in CD19-Cre/iDTR Mice

Demircik, Filiz; Buch, Thorsten; Waisman, Ari

doi:10.1371/journal.pone.0060643

Cited by 14 publications

(10 citation statements)

References 27 publications

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“…DT acts by inhibiting protein synthesis and causing apoptosis of the mouse cells expressing human DTR, whereas the wild‐type cells remain insensitive . Demircik et al . showed successful depletion of B cells in a CD19‐Cre transgenic mouse that was crossed with the iDTR mouse.…”

Section: Resultsmentioning

confidence: 99%

Fluorescence tagging and inducible depletion of PD‐L2–expressing B‐1 B cells in vivo

Lee

Mao

et al. 2015

Annals of the New York Academy of Sciences

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L2pB1 cells are a subpopulation of B-1a B cells that express PD-L2 (programmed death ligand 2) as their unique cell surface marker. In mice, about 50% of peritoneal B-1a cells are L2pB1 cells. The remaining B-1a cells are L2nB1 (PD-L2−) B-1a cells. L2pB1 cells differ from L2nB1 cells in their immunoglobulin repertoire, expression of interleukin 10, and their capacity to phagocytose phosphatidylcholine (PtC). The physiological roles of L2pB1 cells have not been investigated owing to the lack of an animal model that allows for specific depletion of L2pB1 cells. Our data showed that depletion of L2pB1 cells significantly reduces serum anti-phosphorylcholine (PC) IgM level as well as IL-10 expression in the peritoneal cavity. This animal model provides an unequivocal tool for the study of the immune regulatory functions of L2pB1 cells in health and diseases.

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Section: Resultsmentioning

confidence: 99%

Fluorescence tagging and inducible depletion of PD‐L2–expressing B‐1 B cells in vivo

Lee

Mao

et al. 2015

Annals of the New York Academy of Sciences

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“…In order to test whether loss of antral neurons leads to delayed gastric emptying, we established a novel model of focal aganglionosis through ablation of neural crest cells by administration of DT. Cell ablation using Cre‐inducible human DTR was first described in the ablation of T and B cells, and subsequently used to model human diseases . Systemic administration of DT in our Wnt1‐iDTR mice resulted in the mortality of animals within 48 hours.…”

Section: Discussionmentioning

confidence: 99%

Hypoganglionosis in the gastric antrum causes delayed gastric emptying

Baker

Ahmed

Cheng

et al. 2019

Neurogastroenterology Motil

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Background Enteric nervous system (ENS) abnormalities have been implicated in delayed gastric emptying but studies exploring potential treatment options are limited by the lack of an experimental animal model. We examined the ENS abnormalities in the mouse stomach associated with aging, developed a novel model of gastroparesis, and established a new approach to measure gastric emptying. Methods A modified gastric emptying assay was developed, validated in nNOS −/− mice, and tested in mice at multiple ages. Age‐related changes in ENS structure were analyzed by immunohistochemistry. Gastric aganglionosis was generated in Wnt1‐iDTR mice using focal administration of diphtheria toxin (DT) into the anterior antral wall. Key Results Older mice (>5 months) exhibit hypoganglionosis in the gastric antrum and a decreased proportion of nNOS neurons as compared to younger mice (age 5‐7 weeks). This was associated with a significant age‐dependent decrease in liquid and solid gastric emptying. A novel model of gastric antrum hypoganglionosis was established using neural crest‐specific expression of diphtheria toxin receptor. In this model, a significant reduction in liquid and solid gastric emptying is observed. Conclusions & Inferences Older mice exhibit delayed gastric emptying associated with hypoganglionosis and a reduction in nNOS‐expressing neurons in the antrum. The causal relationship between antral hypoganglionosis and delayed gastric emptying was verified using a novel experimental model of ENS ablation. This study provides new information regarding the pathogenesis of delayed gastric emptying and provides a robust model system to study this disease and develop novel treatments.

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“…1), probably owing to the late expression of CD19-Cre during B-cell development [21]. However, spleens of Bcl-3 BOE mice were increased in size resulting in a significant increase in lymphocyte numbers ( Fig.…”

Section: B-cell-specific Overexpression Of Bcl-3mentioning

confidence: 93%

Overexpression of Bcl‐3 inhibits the development of marginal zone B cells

et al. 2013

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The transcription factor Bcl-3 functions as a proto-oncogene via regulation of cell proliferation and apoptosis. Bcl-3 is an atypical member of the IκB family and plays a central role in the immune response through interactions with the NF-κB subunits p50 and p52. To investigate the impact of Bcl-3 on B-cell maturation and regulation, we generated mice that overexpress Bcl-3 specifically in B cells. Interestingly, these mice lack marginal zone B cells and exhibit a significant reduction in the number of B-1 B cells. Further, B cells from these mice are impaired in their proliferative capacity. Our data demonstrate that the overexpression of the transcription factor Bcl-3 inhibits germinal center formation, marginal zone B-cell development, and affects the B-1 B-cell compartment.Keywords: B-1 B cells r Bcl-3 r Marginal zone B cell r NF-κB Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionThe Bcl-3 gene was first identified in a translocation into the Ig alpha locus in various cases of B-cell chronic lymphocytic leukemia [1,2]. The oncogene Bcl-3 encodes for an atypical member of the inhibitor of kappa B (IκB) family of proteins. Although Bcl-3 has high structural homology to the other IκB family members, Bcl-3 fails to inhibit NF-κB molecules in the cytoplasm but instead is a nuclear protein with both activating and repressing functions [3,4]. Specific domains within Bcl-3 can stimulate transcription through interaction with p50 and p52 homodimers [3,5]. So far Bcl-3 has also been implicated in various gene regulatory networks and biological processes [6,7] but its physiological mechanisms of action and in vivo targets remain largely unknown.Correspondence: Dr. Nadine Hövelmeyer e-mail: hoevelme@uni-mainz. de In order to study the role of Bcl-3 in lymphoid malignancies, Tg animals were generated overexpressing Bcl-3 in B and T cells. These mice exhibit splenomegaly and an accumulation of mature B cells in secondary lymphoid organs, but fail to develop lymphoid neoplasms. These mice show an increased response to crosslinking of surface IgM [8]. On the other hand, Bcl-3-deficient mice demonstrate the requirement for Bcl-3 in germinal center (GC) formation and in the production of Ag-specific antibodies [9,10]. Naïve B cells are generally divided into three subsets, B-1 B cells, follicular (FO), and marginal zone (MZ) B cells, whereas MZ B cells play a central role in eliciting Ab response against bloodborn pathogens. These B cells reside within the MZ located outside the marginal sinus and are the juncture of white and red pulp in the spleen. The factors that regulate the homeostasis of MZ B cells are not completely understood. Immature B cells that emigrate * These authors contributed equally to this work. from the bone marrow into the spleen develop through distinct transitional B-cell stages, termed as T1, T2, and T3 [11]. The T2 transitional B cell is thought to be the common precursor for both MZ and FO B cells [12]. FO B cells can b...

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Efficient B Cell Depletion via Diphtheria Toxin in CD19-Cre/iDTR Mice

Cited by 14 publications

References 27 publications

Fluorescence tagging and inducible depletion of PD‐L2–expressing B‐1 B cells in vivo

Fluorescence tagging and inducible depletion of PD‐L2–expressing B‐1 B cells in vivo

Hypoganglionosis in the gastric antrum causes delayed gastric emptying

Overexpression of Bcl‐3 inhibits the development of marginal zone B cells

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