Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders

Brioschi, Simone; Wang, Wei-Le; Peng, Vincent; Wang, Meng; Shchukina, Irina; Greenberg, Zev J.; Bando, Jennifer K.; Jaeger, Natália; Czepielewski, Rafael S.; Swain, Amanda; Mogilenko, Denis A.; Beatty, Wandy L.; Bayguinov, Peter O.; Fitzpatrick, James A.J.; Schuettpelz, Laura G.; Fronick, Catrina C.; Smirnov, Igor; Kipnis, Jonathan; Shapiro, Virginia Smith; Wu, Gregory F.; Gilfillan, Susan; Cella, Marina; Artyomov, Maxim N.; Kleinstein, Steven H.; Colonna, Marco

doi:10.1126/science.abf9277

Cited by 301 publications

(393 citation statements)

References 51 publications

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“…S10C) but lacked Aicda, which is associated with the activation of mature B cells and germinal centre formation. Others have recently presented similar data from the spinal cord and brain meninges of adult mice, and they suggested that the CNS may act as a lymphopoietic niche (Brioschi et al 2021;Cohen et al 2021). The fact that we found proliferating B cells in early neonatal mouse meninges support this notion.…”

Section: Neutrophils Ilcs T Cells and B Cells Are A Minor Fraction Of The Resident Meningeal Leukocytes In Neonatal Micesupporting

confidence: 88%

Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brain

et al. 2021

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The meninges are important for brain development and pathology. Using single-cell RNA sequencing, we have generated the first comprehensive transcriptional atlas of neonatal mouse meningeal leukocytes under normal conditions and after perinatal brain injury. We identified almost all known leukocyte subtypes and found differences between neonatal and adult border-associated macrophages, thus highlighting that neonatal border-associated macrophages are functionally immature with regards to immune responses compared with their adult counterparts. We also identified novel meningeal microglia-like cell populations that may participate in white matter development. Early after the hypoxic-ischemic insult, neutrophil numbers increased and they exhibited increased granulopoiesis, suggesting that the meninges are an important site of immune cell expansion with implications for the initiation of inflammatory cascades after neonatal brain injury. Our study provides a single-cell resolution view of the importance of meningeal leukocytes at the early stage of development in health and disease.

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Section: Neutrophils Ilcs T Cells and B Cells Are A Minor Fraction Of The Resident Meningeal Leukocytes In Neonatal Micesupporting

confidence: 88%

Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brain

et al. 2021

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“…Additionally, it has recently been reported that the majority of myeloid cells in the meninges are derived from the skull bone marrow both in homeostatic and pathological states (72). Of note as well is the role of the skull bone marrow as a source of B cells to the meninges, with these developing B cells travelling via the direct vascular network to the meninges to complete their maturation (73). It is worth noting however that the role of B cells in AD pathogenesis still remains elusive.…”

Section: Meninges Choroid Plexus and Skull Bone Marrowmentioning

confidence: 99%

The Impact of Ageing on the CNS Immune Response in Alzheimer’s Disease

Chee

Solito

2021

Front. Immunol.

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disease strongly associated with increasing age. Neuroinflammation and the accumulation of amyloid protein are amongst the hallmarks of this disease and most translational research to date has focused on targeting these two processes. However, the exact etiology of AD remains to be fully elucidated. When compared alongside, the immune response in AD closely resembles the central nervous system (CNS) immune changes seen in elderly individuals. It is possible that AD is a pathological consequence of an aged immune system secondary to chronic stimulation by a previous or ongoing insult. Pathological changes like amyloid accumulation and neuronal cell death may reflect this process of immunosenescence as the CNS immune system fails to maintain homeostasis in the CNS. It is likely that future treatments designed to modulate the aged immune system may prove beneficial in altering the disease course. The development of new tests for appropriate biomarkers would also be essential in screening for patients most likely to benefit from such treatments.

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“…Moreover, when capacity for testing is limited early in an epidemic, as with COVID-19, it can be targeted towards regions, populations, and settings most likely to have high community spread when social contact patterns are known, facilitating identification of both mildly symptomatic and asymptomatic carriers and preventing transmission by super-spreaders. When vaccines become available, a lack of accurate information impacts optimal vaccine distribution as well as vaccination booster schedules [ 14 ]. In order to fill this information gap, we describe and quantify US social contact patterns using data from the Bureau of Labor Statistics’ American Time Use Survey (ATUS), 2003–2018.…”

Section: Introductionmentioning

confidence: 99%

Analyzing the demographic, spatial, and temporal factors influencing social contact patterns in U.S. and implications for infectious disease spread

et al. 2021

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Background Diseases such as COVID-19 are spread through social contact. Reducing social contacts is required to stop disease spread in pandemics for which vaccines have not yet been developed. However, existing data on social contact patterns in the United States (U.S.) is limited. Method We use American Time Use Survey data from 2003–2018 to describe and quantify the age-pattern of disease-relevant social contacts. For within-household contacts, we construct age-structured contact duration matrices (who spends time with whom, by age). For both within-household and non-household contacts, we also estimate the mean number and duration of contact by location. We estimate and test for differences in the age-pattern of social contacts based on demographic, temporal, and spatial characteristics. Results The mean number and duration of social contacts vary by age. The biggest gender differences in the age-pattern of social contacts are at home and at work; the former appears to be driven by caretaking responsibilities. Non-Hispanic Blacks have a shorter duration of contact and fewer social contacts than non-Hispanic Whites. This difference is largely driven by fewer and shorter contacts at home. Pre-pandemic, non-Hispanic Blacks have shorter durations of work contacts. Their jobs are more likely to require close physical proximity, so their contacts are riskier than those of non-Hispanic Whites. Hispanics have the highest number of household contacts and are also more likely to work in jobs requiring close physical proximity than non-Hispanic Whites. With the exceptions of work and school contacts, the duration of social contact is higher on weekends than on weekdays. Seasonal differences in the total duration of social contacts are driven by school-aged respondents who have significantly shorter contacts during the summer months. Contact patterns did not differ by metro status. Age patterns of social contacts were similar across regions. Conclusion Social contact patterns differ by age, race and ethnicity, and gender. Other factors besides contact patterns may be driving seasonal variation in disease incidence if school-aged individuals are not an important source of transmission. Pre-pandemic, there were no spatial differences in social contacts, but this finding has likely changed during the pandemic.

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Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders

Cited by 301 publications

References 51 publications

Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brain

Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brain

The Impact of Ageing on the CNS Immune Response in Alzheimer’s Disease

Analyzing the demographic, spatial, and temporal factors influencing social contact patterns in U.S. and implications for infectious disease spread

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