BOB.1/OBF.1 - A Critical Regulator of B Cell Function

Brunner, Cornelia; Wirth, Thomas

doi:10.2174/157339506775471901

Cited by 10 publications

(15 citation statements)

References 100 publications

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“…We reviewed the literature and made an up-to-date POU2AF1 downstream gene list (not shown). Consistent with the literature 4-6,19 , POU2AF1 induced significant expression differences of known POU2AF1 downstream genes compared to lenti-RFP and uninfected controls (Figure S2), including ID2 19 , ID3 19 , HLA-DRA 20 , IL6 21 , S100A10 22 and KCNN4 22 . Unsupervised hierarchical analysis of the top 50 genes up-regulated by POU2AF1 clearly segregated the lenti-POU2AF1 group from the control groups (lenti-RFP and uninfected; Figure 2C).…”

Section: Resultssupporting

confidence: 90%

“…Interestingly, in both the initial and in a validation airway epithelium microarray cohort 23,26 , expression of POU2AF1 and its downstream host defense genes segregated smokers and nonsmokers into two populations (Figure 4F, 4G), suggesting smoking disorders the POU2AF1-regulated host defense gene network in the human airway epithelium. Based on these data, we conclude that, in addition to previous known stimuli 4,6 , POU2AF1 gene expression is also regulated by cigarette smoking, and impaired expression of POU2AF1 likely contributes to the disordered airway host defense associated with smoking.…”

Section: Resultsmentioning

confidence: 73%

“…Unexpectedly, in the process of seeking novel host defense regulators in the human airway epithelium, we detected expression in airway epithelium RNA-Seq data of POU2AF1, a transcription cofactor generally regarded as lymphocyte-restricted 4,6 (Figure S1A). The expression of POU2AF1 in the human airway epithelium has an average of 6 RPKM, close to the average expression level of all the transcription factors in the airway epithelium (Figure S1B).…”

Section: Resultsmentioning

confidence: 98%

“…In addition to modulation of the IgG gene in B cells, POU2AF1 has multiple known downstream genes with diverse functions in lymphocytes, such as cellular metabolism, cell survival, surface receptors, ion transport and cell adhesion 4-6 . Many of these genes have roles in host defense.…”

Section: Resultsmentioning

confidence: 99%

“…In a genome-wide RNA sequencing analysis of human airway epithelium gene expression, we observed expression of POU domain class 2-associating factor 1 (POU2AF1; also named OCA-B, OBF-1 and BOB.1), a gene previously considered to be expressed specifically in lymphocytes, where it functions as a co-activator of octamer-binding OCT1 and OCT2 transcription factors to regulate immunoglobin expression and other host defense-related genes 4-6 . POU2AF1 has no intrinsic DNA binding activity, but by recognizing the POU domain of OCT1 and OCT2, it plays an essential role in B-cell responses to antigens and is required for the formation of germinal centers 7-9 .…”

Section: Introductionmentioning

confidence: 99%

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POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes

Zhou

Brekman

Zuo

et al. 2016

The Journal of Immunology

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In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU2AF1, a known transcription co-factor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of up-regulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation and analysis of differentiating single basal cell clones. Lentivirus-mediated up-regulation of POU2AF1 in airway basal cells induced up-regulation of host defense genes, including MX1, IFIT3, IFITM and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a “host defense tone” even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes

Zhou

Brekman

Zuo

et al. 2016

The Journal of Immunology

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NF‐κB‐dependent signals control BOB.1/OBF.1 and Oct2 transcriptional activity in B cells

et al. 2015

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The transcriptional co‐activator BOB.1/OBF.1 is crucial for Octamer‐driven transcription in B cells. BOB.1/OBF.1‐deficiency leads to tremendous defects in B‐cell development and function. Therefore, in the past research focused on the identification of BOB.1/OBF.1 target genes. However, the regulation of BOB.1/OBF.1 expression itself is poorly understood. Here we show that in B cells NF‐κB as well as to some extent NFAT proteins are involved in the activation of basal as well as inducible BOB.1/OBF.1 expression by direct binding to the BOB.1/OBF.1 promoter. Moreover, the analysis of different inducers of NF‐κB, like several TLR ligands, TNF‐α, BAFF, or LTα1β2, revealed that both the canonical and noncanonical NF‐κB pathways are involved in the induction of BOB.1/OBF.1 gene. The identification of so far unknown inducers that regulate BOB.1/OBF.1 expression in B cells provides novel insights in the potential function of BOB.1/OBF.1 during different aspects of B‐cell development and function.

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BOB.1/OBF.1 is required during B‐cell ontogeny for B‐cell differentiation and germinal center function

et al. 2021

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BOB.1/OBF.1 is a lymphocyte‐specific transcriptional co‐activator of octamer‐dependent transcription. It regulates the expression of genes important for lymphocyte physiology together with the Oct‐1 and Oct‐2 transcription factors. So far, BOB.1/OBF.1 has been studied in conventional knockout mice, whereby a function of BOB.1/OBF.1 in B but also in T cells was described. The main characteristic of BOB.1/OBF.1‐deficient mice is the complete absence of germinal centers. However, it is entirely unsolved at which stage of B‐cell development BOB.1/OBF.1 expression is essential for germinal center formation. Still, it is not known whether defects observed late in B‐cell development of BOB.1/OBF.1‐deficient mice are merely a consequence of defective early B‐cell development. To answer the question, whether BOB.1/OBF.1 expression is required before or during the process of germinal center formation, we established a mouse system, which allows the conditional deletion of BOB.1/OBF.1 at different stages of B‐cell development. Our data reveal a requirement for BOB.1/OBF.1 during both early antigen‐independent and late antigen‐dependent B‐cell development, and further a requirement for efficient germinal center reaction during complete B‐cell ontogeny. By specifically deleting BOB.1/OBF.1 in germinal center B cells, we provide evidence that the failure to form germinal centers is a germinal center B‐cell intrinsic defect and not exclusively a consequence of defective early B‐cell maturation.

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BOB.1/OBF.1 - A Critical Regulator of B Cell Function

Abstract: The transcriptional coactivator BOB.1/OBF.

Cited by 10 publications

References 100 publications

POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes

POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes

NF‐κB‐dependent signals control BOB.1/OBF.1 and Oct2 transcriptional activity in B cells

BOB.1/OBF.1 is required during B‐cell ontogeny for B‐cell differentiation and germinal center function

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