scholarly journals Unique Transcriptome Changes in Peripheral B Cells Revealed by Comparing Age Groups From Naive or Vaccinated Mice, Including snoRNA and Cdkn2a

2020 ◽  
Vol 75 (12) ◽  
pp. 2326-2332
Author(s):  
Robin L Baudier ◽  
Kevin J Zwezdaryk ◽  
Malwina Czarny-Ratajczak ◽  
Lauren H Kodroff ◽  
Deborah E Sullivan ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Middle Age ◽  
Age Groups ◽  
Principal Component ◽  
Cell Cycle Checkpoint ◽  
Vaccine Responses ◽  
Age Related ◽  
Vaccination History ◽  
Canonical Pathways

Abstract Aging is associated with a decline in immune function that is not fully understood including vaccine failure. Here we report transcriptomic analysis on B cells from naive or influenza-vaccinated mice of 3 ages: young (15–23 weeks), middle-aged (63–81 weeks), and old mice (103–119 weeks). Our goal was expression profiling of B cells by age and history of vaccination to identify novel changes at the transcriptome level. We observed waning vaccine responses with age. In B cell transcripts, age and vaccination history were both important with notable differences observed in conducted analyses (eg, principal component, gene set enrichment, differentially expressed [DE] genes, and canonical pathways). Only 39 genes were significantly DE with age irrespective of vaccine history. This included age-related changes to box C/D small nucleolar (sno) RNAs, Snord123 and Snord1a. Box C/D snoRNAs regulate rRNAs through methylation and are linked to neurodegenerative, inflammatory, and cancer diseases but not specifically B cells or age. Canonical pathway changes implicated with age irrespective of vaccination history included EIF2, mTOR signaling, p53, Paxillin, and Tec kinase signaling pathways as well as cell cycle checkpoint. Importantly, we identified DE genes and pathways that were progressively altered starting in middle-age (eg, signaling by Rho family GTPases) or only altered in middle-age (eg, sphingosine-1-phosphate signaling), despite minimal differences in the ability of these mice to respond to vaccination compared to younger mice. Our results indicate the importance of vaccination or immune stimulation and analyses of multiple age ranges for aging B cell studies and validate an experimental model for future studies.

scholarly journals Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues

2020 ◽  
Author(s):  
Fan Yang ◽  
Sandra C. A. Nielsen ◽  
Ramona A. Hoh ◽  
Ji-Yeun Lee ◽  
Tho D. Pham ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Clonal Evolution ◽  
Age Groups ◽  
Immune Memory ◽  
Lymphoid Tissues ◽  
Specific Class ◽  
Cell Memory ◽  
Age Related ◽  
B Cell Memory

AbstractVaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells encoding humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults’ convergent clones often express mutated IgM or IgD in blood and are class-switched in lymphoid tissues; in contrast, children have abundant class-switched convergent clones in blood. Consistent with serological reports, pre-pandemic children had class-switched convergent clones to SARS-CoV-2, enriched in cross-reactive clones for seasonal coronaviruses, while adults showed few such clones in blood or lymphoid tissues. These results extend age-related and anatomical mapping of human humoral pathogen-specific immunity.One Sentence SummaryChildren have elevated frequencies of pathogen-specific class-switched memory B cells, including SARS-CoV-2-binding clones.

scholarly journals Metabolic defects in splenic B cell compartments from patients with liver cirrhosis

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Man Huang ◽  
Xiaoju Liu ◽  
Haocheng Ye ◽  
Xin Zhao ◽  
Juanjuan Zhao ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Rna Seq ◽  
Vaccine Responses ◽  
Cell Functions ◽  
Metabolic Defects ◽  
Cell Compartments ◽  
Cirrhotic Patients

Abstract Liver cirrhosis is associated with defective vaccine responses and increased infections. Dysregulated B cell compartments in cirrhotic patients have been noticed but not well characterized, especially in the spleen. Here, we comprehensively investigated B cell perturbations from the spleens and peripheral blood of cirrhotic patients. We found that liver cirrhosis significantly depleted both switched and nonswitched splenic memory B cells, which was further confirmed histologically. Bulk RNA-seq revealed significant metabolic defects as the potential mechanism for the impaired splenic B cell functions. Functionally, the splenic memory B cells from cirrhotic patients showed strong metabolic defects and reduced proliferation compared with those from healthy controls. Thus, liver cirrhosis extensively disturbs the splenic and peripheral B cell compartments, which may contribute to defective humoral immunity during liver cirrhosis.

DEVELOPMENT OF POLYPLOIDY IN B-CELLS OF NORMAL AND DIABETIC MICE

1979 ◽  
Vol 90 (2) ◽  
pp. 295-306 ◽  
Author(s):  
M. N. Pohl ◽  
F. J. Swartz
Keyword(s):  
B Cells ◽  
B Cell ◽  
Age Groups ◽  
Particle Size Analysis ◽  
Nuclear Volume ◽  
Size Analysis ◽  
Disease Symptoms ◽  
Aldehyde Fuchsin ◽  
The Relationship ◽  
Diabetic Syndrome

ABSTRACT This study was designed to clarify the relationship between pancreatic B-cell polyploidization and the progress of the diabetic syndrome in genetically diabetic (C57BL/Ks-db/db) and normal control mice (C57BL/KsJ) of matched age groups. Nuclear volume was confirmed to be a proper index of the polyploid class of the B-cell by correlation with Feulgen-DNA content as measured by microdensitometry. Nuclei of B-cells, identified by aldehyde fuchsin positive cytoplasmic granules, were traced by camera lucida and their volumes determined by semiautomatic particle size analysis. Six age groups were studied: 4.5, 7, 9.5, 12, 14.5 and 17 weeks. The major conclusions are: 1) The percentage of tetraploid nuclei in normal mice is consistently between 1.0 and 2.0% from 4.5 to 14.5 weeks of age and increases to approximately 3.0 % at 17 weeks of age; however, further studies are required to determined the significance of this increase; 2) in all age groups studied, percentages of polyploid nuclei are significantly greater in diabetic than in control mice; 3) the percentage of tetraploid nuclei in diabetic animals is elevated 220 % over controls at 4.5 weeks of age, remains constant until 12 weeks (while other parameters such as blood glucose level and body weight continue to rise) and increases significantly between 12 and 14.5 weeks of age. Implications of both the increased polyploidy observed at the onset of disease symptoms, and the dramatic increase occurring during the later stages of the disease, are discussed.

The structure of time perspective: Age-related differences in Poland

2016 ◽  
Vol 28 (1) ◽  
pp. 5-32 ◽  
Author(s):  
Malgorzata Sobol-Kwapinska ◽  
Aneta Przepiorka ◽  
Philip P Zimbardo
Keyword(s):  
Factor Structure ◽  
Time Perspective ◽  
Developmental Change ◽  
Age Groups ◽  
Principal Component ◽  
Age Related ◽  
Confirmatory Factor ◽  
Polish Version ◽  
Separate Factor ◽  
Three Factor

The purpose of the paper is to present the main findings on the factor structure of time perspective measured using the Polish version of the Zimbardo Time Perspective Inventory (Zimbardo and Boyd, 1999) in different age groups. A total of 2789 adults took part in the study. Confirmatory factor analysis of Zimbardo Time Perspective Inventory items was conducted in a group of respondents aged 18–78 years to verify the original five-factor structure. Separate principal component analyses were carried out for three age groups: 18–27, 28–39, and 40–65 years old. In the group of students, a fairly clear five-factor structure of time perspective was found. In the group of the oldest respondents, a three-factor structure emerged, which can be described as follows: Past-Negative combined with Present-Fatalistic, Past-Positive combined with Future, and a separate factor corresponding to the Present-Hedonistic scale. Differences in the factor structure of time perspective were interpreted in the context of developmental change.

scholarly journals Fate mapping quantifies the dynamics of B cell development and activation throughout life

2019 ◽  
Author(s):  
Melissa Verheijen ◽  
Sanket Rane ◽  
Claire Pearson ◽  
Andrew J. Yates ◽  
Benedict Seddon
Keyword(s):  
B Cells ◽  
B Cell ◽  
Integrative Approach ◽  
Fate Mapping ◽  
Cell Lineages ◽  
Age Related ◽  
Mapping System ◽  
A Cell ◽  
Transitional Cells ◽  
B Cell Homeostasis

SummaryFollicular mature (FM) and germinal centre (GC) B cells underpin humoral immunity but the dynamics of their generation and maintenance are not clearly defined. Here we exploited a fate-mapping system in mice that tracks B cells as they develop into peripheral subsets, together with a cell division fate reporter mouse and mathematical models. We find that FM cells are kinetically homogeneous, recirculate freely, continually replenished from transitional populations, and self-renew rarely. In contrast, GC B cell lineages persist for weeks with rapid turnover and site-specific dynamics. Those in the spleen derive from transitional cells and are kinetically homogeneous, while those in lymph nodes derive from FM B cells and comprise both transient and persistent clones. These differences likely derive from the nature of antigen exposure at the different sites. Our integrative approach also reveals how the host environment drives cell-extrinsic, age-related changes in B cell homeostasis.

scholarly journals A single-cell atlas of lymphocyte adaptive immune repertoires and transcriptomes reveals age-related differences in convalescent COVID-19 patients

2021 ◽  
Author(s):  
Florian Bieberich ◽  
Rodrigo Vazquez-Lombardi ◽  
Alexander Yermanos ◽  
Roy A. Ehling ◽  
Derek M. Mason ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Somatic Hypermutation ◽  
Critical Role ◽  
Young Patients ◽  
Cell Receptors ◽  
Adaptive Immune ◽  
Age Related

AbstractCOVID-19 disease outcome is highly dependent on adaptive immunity from T and B lymphocytes, which play a critical role in the control, clearance and long-term protection against SARS-CoV-2. To date, there is limited knowledge on the composition of the T and B cell immune receptor repertoires [T cell receptors (TCRs) and B cell receptors (BCRs)] and transcriptomes in convalescent COVID-19 patients of different age groups. Here, we utilize single-cell sequencing (scSeq) of lymphocyte immune repertoires and transcriptomes to quantitatively profile the adaptive immune response in COVID-19 patients of varying age. We discovered highly expanded T and B cells in multiple patients, with the most expanded clonotypes coming from the effector CD8+ T cell population. Highly expanded CD8+ and CD4+ T cell clones show elevated markers of cytotoxicity (CD8: PRF1, GZMH, GNLY; CD4: GZMA), whereas clonally expanded B cells show markers of transition into the plasma cell state and activation across patients. By comparing young and old convalescent COVID-19 patients (mean ages = 31 and 66.8 years, respectively), we found that clonally expanded B cells in young patients were predominantly of the IgA isotype and their BCRs had incurred higher levels of somatic hypermutation than elderly patients. In conclusion, our scSeq analysis defines the adaptive immune repertoire and transcriptome in convalescent COVID-19 patients and shows important age-related differences implicated in immunity against SARS-CoV-2.

scholarly journals Age-Associated Differences of Modules and Hubs in Brain Functional Networks

2021 ◽  
Vol 12 ◽  
Author(s):  
Yinghui Zhang ◽  
Yin Wang ◽  
Nan Chen ◽  
Man Guo ◽  
Xiuzhen Wang ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Middle Age ◽  
Age Groups ◽  
Young Group ◽  
Brain Dysfunction ◽  
Modular Organization ◽  
Functional Networks ◽  
Inverse Association ◽  
Cross Sectional ◽  
Age Related

Healthy aging is usually accompanied by changes in the functional modular organization of the human brain, which may result in the decline of cognition and underlying brain dysfunction. However, the relationship between age-related brain functional modular structure differences and cognition remain debatable. In this study, we investigated the age-associated differences of modules and hubs from young, middle and old age groups, using resting-state fMRI data from a large cross-sectional adulthood sample. We first divided the subjects into three age groups and constructed an individual-level network for each subject. Subsequently, a module-guided group-level network construction method was applied to form a weighted network for each group from which functional modules were detected. The intra- and inter-modular connectivities were observed negatively correlated with age. According to the detected modules, we found the number of connector hubs in the young group was more than middle-age and old group, while the quantity of provincial hubs in middle-age group was discovered more than other two groups. Further ROI-wise analysis shows that different hubs have distinct age-associated trajectories of intra- and inter-modular connections, which suggests the different types of topological role transitions in functional networks across age groups. Our results indicated an inverse association between functional segregation/integration with age, which demonstrated age-associated differences in communication effeciency. This study provides a new perspective and useful information to better understand the normal aging of brain networks.

scholarly journals Activated PIK3CD drives innate B cell expansion yet limits B cell–intrinsic immune responses

2018 ◽  
Vol 215 (10) ◽  
pp. 2485-2496 ◽  
Author(s):  
Michelle N. Wray-Dutra ◽  
Fahd Al Qureshah ◽  
Genita Metzler ◽  
Mohamed Oukka ◽  
Richard G. James ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Plasma Cells ◽  
Recurrent Infection ◽  
Vaccine Responses ◽  
And Function ◽  
Natural Igm ◽  
The Impact

Activated PI3K-delta syndrome (APDS) is an immunodeficiency caused by gain-of-function mutations in PIK3CD. This disease exhibits complex immune phenotypes including increased IgM, recurrent infection, and impaired vaccine responses. To better understand the impact of B cells in this disease, we generated an inducible model of the common APDS mutation (hPIK3CD-E1021K; referred to as aPIK3CD) and intercrossed these mice with B cell–specific Cre models. Mb1-aPIK3CD mice exhibited bone marrow B lymphopenia and, conversely, expansion of the peripheral innate B1a and MZ B cell compartments. aPIK3CD B cells manifest increased pS6 and increased survival at several stages, without alterations in cycling, and baseline increases in plasma cells, natural IgM, and IgG3. Finally, Mb1-aPIK3CD mice exhibited blunted T cell–independent immune responses, and both AID- and CD21-aPIK3CD mice displayed reduced class-switched antibodies following T cell–dependent immunization. Thus, aPIK3CD alters B cell development and function and is counter-productive during immune responses, providing insight into B cell–intrinsic contributions to the APDS phenotype.

scholarly journals Noxa mediates p18INK4c cell-cycle control of homeostasis in B cells and plasma cell precursors

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2179-2188 ◽  
Author(s):  
Jamieson Bretz ◽  
Josefina Garcia ◽  
Xiangao Huang ◽  
Lin Kang ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Plasma Cells ◽  
Cell Cycle Control ◽  
Cell Cycle Checkpoint ◽  
G1 Arrest ◽  
B Cell Activation ◽  
A Minor

Abstract Inhibition of Cdk4/Cdk6 by p18INK4c (p18) is pivotal for generation of noncycling immunoglobulin (Ig)-secreting plasma cells (PCs). In the absence of p18, CD138+ plasmacytoid cells continue to cycle and turnover rapidly, suggesting that p18 controls PC homeostasis. We now show that p18 selectively acts in a rare population of rapidly cycling CD138hi/B220hi intermediate PCs (iPCs). While retaining certain B-cell signatures, iPCs are poised to differentiate to end-stage PCs although the majority undergo apoptosis. p18 is dispensable for the development of the PC transcriptional circuitry, and Blimp-1 and Bcl-6 are expressed fully and mutually exclusively in individual iPCs. However, a minor proportion of iPCs express both, and they are preferentially protected by p18 or Bcl-xL overexpression, consistent with expansion of the iPC pool by Bcl-xL overexpression, or loss of proapoptotic Bim or Noxa. Expression of Noxa is induced during B-cell activation, peaks in iPCs, and selectively repressed by p18. It is required to promote apoptosis of cycling B cells, especially in the absence of p18. These findings define the first physiologic function for Noxa and suggest that by repressing Noxa, induction of G1 arrest by p18 bypasses a homeostatic cell-cycle checkpoint in iPCs for PC differentiation.

scholarly journals Isometric Strength in Volleyball Players of Different Age: A Multidimensional Model

2020 ◽  
Vol 10 (12) ◽  
pp. 4107 ◽  
Author(s):  
Nikola Majstorović ◽  
Milivoj Dopsaj ◽  
Vladimir Grbić ◽  
Zoran Savić ◽  
Aleksandar Vićentijević ◽  
...  
Keyword(s):  
Age Groups ◽  
Principal Component ◽  
Isometric Strength ◽  
Age Related ◽  
Strength Tests ◽  
Volleyball Players ◽  
Physical Abilities ◽  
Single Score ◽  
Male Subjects

Physical abilities modelling has a profound connection with long-term athlete development and talent identification. There is not enough data to support evidence about age-related changes in volleyball players’ isometric strength. This study aimed to define the age-related model of volleyball players multidimensional muscles’ contractile characteristics. The participants were divided according to gender (male n = 112, female n = 371) and according to age into four groups: under 15 (U15), under 17 (U17), under 19 (U19), and under 21 (U21) years old. Participants performed three isometric strength tests: handgrip, lumbar extensors, and ankle extensors. Maximal force and rate of force development results from all three tests were transformed into a single Score value as a representation of contractile potentials using principal component analysis. The main findings were that Score values of both genders showed significant differences between age groups (male: F = 53.17, p < 0.001; Female: F = 41.61, p < 0.001). Trends of those yearly changes were slightly more balanced for female subjects (3.9%) compared to male subjects (6.3%). These findings could help in strength training adjustments when working with volleyball players of a certain age, and enable coaches to detect ones that stand out positively, considering them as strong in regard to their age.

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