The impact of hypoxia on B cells in COVID-19

Kotagiri, Prasanti; Mescia, Federica; Hanson, Aimee L.; Turner, Lorinda; Bergamaschi, Laura; Peñalver, Ana; Richoz, Nathan; Moore, Stephen D.; Ortmann, Brian; Dunmore, Benjamin J.; Morgan, Michael D.; Tuong, Zewen Kelvin; Göttgens, Berthold; Toshner, Mark; Hess, Christoph; Maxwell, Patrick H.; Clatworthy, Menna R.; Nathan, James A.; Bradley, John R.; Lyons, Paul; Burrows, Natalie; Smith, Kenneth G. C.

doi:10.1016/j.ebiom.2022.103878

Cited by 20 publications

(15 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One explanation for this could be the need for nutrients, energy and oxygen during somatic hypermutation and proliferation of B-cells during an inflammatory state, which exceeds the capabilities of a less dense capillary bed ( 5 ). In addition, the oxygen supply seems to play an important role for proper B-cell function and arrangement, as recent studies claim serve B-cell abnormalities during hypoxia in COVID-19 ( 80 ). Evidence for another scenario could be found in the migration and homing of lymphocytes through HEVs.…”

Section: Discussionmentioning

confidence: 97%

Three-dimensional analyses of vascular network morphology in a murine lymph node by X-ray phase-contrast tomography with a 2D Talbot array

et al. 2022

View full text Add to dashboard Cite

With growing molecular evidence for correlations between spatial arrangement of blood vasculature and fundamental immunological functions, carried out in distinct compartments of the subdivided lymph node, there is an urgent need for three-dimensional models that can link these aspects. We reconstructed such models at a 1.84 µm resolution by the means of X-ray phase-contrast imaging with a 2D Talbot array in a short time without any staining. In addition reconstructions are verified in immunohistochemistry staining as well as in ultrastructural analyses. While conventional illustrations of mammalian lymph nodes depict the hilus as a definite point of blood and lymphatic vessel entry and exit, our method revealed that multiple branches enter and emerge from an area that extends up to one third of the organ’s surface. This could be a prerequisite for the drastic and location-dependent remodeling of vascularization, which is necessary for lymph node expansion during inflammation. Contrary to corrosion cast studies we identified B-cell follicles exhibiting a two times denser capillary network than the deep cortical units of the T-cell zone. In addition to our observation of high endothelial venules spatially surrounding the follicles, this suggests a direct connection between morphology and B-cell homing. Our findings will deepen the understanding of functional lymph node composition and lymphocyte migration on a fundamental basis.

show abstract

Section: Discussionmentioning

confidence: 97%

Three-dimensional analyses of vascular network morphology in a murine lymph node by X-ray phase-contrast tomography with a 2D Talbot array

et al. 2022

View full text Add to dashboard Cite

show abstract

“…(e) Last but not least, the SARS-CoV-2 virus, an important threat to global public health, has been reported to cause systemic hypoxia and a notable reduction in B cell numbers. Hypoxia contributes to the pronounced and persistent B cell pathology of acute SARS-CoV-2 ( 105 ). Evaluating the effect of early oxygen therapy on B cell immunodeficiency provides a reference for the treatment of similar major infectious diseases ( 106 , 107 ).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia and hypoxia-inducible factor signals regulate the development, metabolism, and function of B cells

Zhang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Hypoxia is a common hallmark of healthy tissues in physiological states or chronically inflamed tissues in pathological states. Mammalian cells sense and adapt to hypoxia mainly through hypoxia-inducible factor (HIF) signaling. Many studies have shown that hypoxia and HIF signaling play an important regulatory role in development and function of innate immune cells and T cells, but their role in B cell biology is still controversial. B cells experience a complex life cycle (including hematopoietic stem cells, pro-B cells, pre-B cells, immature B cells, mature naïve B cells, activated B cells, plasma cells, and memory B cells), and the partial pressure of oxygen (PO2) in the corresponding developmental niche of stage-specific B cells is highly dynamic, which suggests that hypoxia and HIF signaling may play an indispensable role in B cell biology. Based on the fact that hypoxia niches exist in the B cell life cycle, this review focuses on recent discoveries about how hypoxia and HIF signaling regulate the development, metabolism, and function of B cells, to facilitate a deep understanding of the role of hypoxia in B cell-mediated adaptive immunity and to provide novel strategies for vaccine adjuvant research and the treatment of immunity-related or infectious diseases.

show abstract

“…Plasma cells were significantly increased in recovering COVID-19 patients, while naïve B cells were significantly decreased ( Wen et al., 2020 ). Lower B-cell counts might lead to poor virus elimination and severe disease ( Kotagiri et al., 2022 ). More research could be conducted to examine the long-term dynamics of B cells and SARS-CoV-2-specific antibodies produced in vivo .…”

Section: Discussionmentioning

confidence: 99%

Characteristics of COVID-19 Patients With SARS-CoV-2 Positivity in Feces

Shi

Zhu

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

BackgroundSARS-CoV-2 is highly contagious and poses a great threat to epidemic control and prevention. The possibility of fecal-oral transmission has attracted increasing concern. However, viral shedding in feces has not been completely investigated.MethodsThis study retrospectively reviewed 97 confirmed coronavirus disease 2019 (COVID-19) patients hospitalized at the First Affiliated Hospital, School of Medicine, Zhejiang University, from January 19 to February 17, 2020. SARS-CoV-2 RNA in samples of sputum, nasopharyngeal or throat swabs, bronchoalveolar lavage and feces was detected by real-time reverse transcription polymerase chain reaction (RT–PCR). Clinical characteristics and parameters were compared between groups to determine whether fecal RNA was positive.ResultsThirty-four (35.1%) of the patients showed detectable SARS-CoV-2 RNA in feces, and 63 (64.9%) had negative detection results. The median time of viral shedding in feces was approximately 25 days, with the maximum time reaching 33 days. Prolonged fecal-shedding patients showed longer hospital stays. Those patients for whom fecal viral positivity persisted longer than 3 weeks also had lower plasma B-cell counts than those patients in the non-prolonged group [70.5 (47.3-121.5) per μL vs. 186.5 (129.3-376.0) per μL, P = 0.023]. Correlation analysis found that the duration of fecal shedding was positively related to the duration of respiratory viral shedding (R = 0.70, P < 0.001) and negatively related to peripheral B-cell counts (R = -0.44, P < 0.05).ConclusionsCOVID-19 patients who shed SARS-CoV-2 RNA in feces presented similar clinical characteristics and outcomes as those who did not shed SARS-CoV-2 RNA in feces. The prolonged presence of SARS-CoV-2 nucleic acids in feces was highly correlated with the prolonged shedding of SARS-CoV-2 RNA in the respiratory tract and with lower plasma B-cell counts.

show abstract

The impact of hypoxia on B cells in COVID-19

Cited by 20 publications

References 36 publications

Three-dimensional analyses of vascular network morphology in a murine lymph node by X-ray phase-contrast tomography with a 2D Talbot array

Three-dimensional analyses of vascular network morphology in a murine lymph node by X-ray phase-contrast tomography with a 2D Talbot array

Hypoxia and hypoxia-inducible factor signals regulate the development, metabolism, and function of B cells

Characteristics of COVID-19 Patients With SARS-CoV-2 Positivity in Feces

Contact Info

Product

Resources

About