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.

scholarly journals Evidence for Selective Transformation of Autoreactive Immature Plasma Cells in Mice Deficient in Fasl

2004 ◽  
Vol 200 (11) ◽  
pp. 1467-1478 ◽  
Author(s):  
Jian Qiao Zhang ◽  
Cheryl Okumura ◽  
Thomas McCarty ◽  
Min Sun Shin ◽  
Partha Mukhopadhyay ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Gene Repertoire ◽  
Altered Expression ◽  
Autoreactive B Cells ◽  
Systemic Autoimmunity ◽  
The Relationship

Germline mutations in Fas and Fasl induce nonmalignant T cell hyperplasia and systemic autoimmunity and also greatly increase the risk of B cell neoplasms. B lymphomas occurring in Fasl mutant (gld) mice usually are immunoglobulin (Ig) isotype switched, secrete Ig, and are plasmacytoid in appearance but lack Myc translocations characteristic of other plasma cell (PC) neoplasms. Here, we explore the relationship between B cell autoreactivity and transformation and use gene expression profiling to further classify gld plasmacytoid lymphomas (PLs) and to identify genes of potential importance in transformation. We found that the majority of PLs derive from antigen-experienced autoreactive B cells producing antinuclear antibody or rheumatoid factor and exhibit the skewed Ig V gene repertoire and Ig gene rearrangement patterns associated with these specificities. Gene expression profiling revealed that both primary and transplanted PLs share a transcriptional profile that places them at an early stage in PC differentiation and distinguishes them from other B cell neoplasms. In addition, genes were identified whose altered expression might be relevant in lymphomagenesis. Our findings provide a strong case for targeted transformation of autoreactive B cells in gld mice and establish a valuable model for understanding the relationship between systemic autoimmunity and B cell neoplasia.

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 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 Positive selection of the peripheral B cell repertoire in gut-associated lymphoid tissues

2004 ◽  
Vol 201 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Ki-Jong Rhee ◽  
Paul J. Jasper ◽  
Periannan Sethupathi ◽  
Malathy Shanmugam ◽  
Dennis Lanning ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Intestinal Microflora ◽  
Molecular Mechanisms ◽  
Amino Acid Sequences ◽  
Lymphoid Tissues ◽  
Antibody Repertoire ◽  
Cell Repertoire ◽  
B Cell Repertoire ◽  
The Relationship

Gut-associated lymphoid tissues (GALTs) interact with intestinal microflora to drive GALT development and diversify the primary antibody repertoire; however, the molecular mechanisms that link these events remain elusive. Alicia rabbits provide an excellent model to investigate the relationship between GALT, intestinal microflora, and modulation of the antibody repertoire. Most B cells in neonatal Alicia rabbits express VHn allotype immunoglobulin (Ig)M. Within weeks, the number of VHn B cells decreases, whereas VHa allotype B cells increase in number and become predominant. We hypothesized that the repertoire shift from VHn to VHa B cells results from interactions between GALT and intestinal microflora. To test this hypothesis, we surgically removed organized GALT from newborn Alicia pups and ligated the appendix to sequester it from intestinal microflora. Flow cytometry and nucleotide sequence analyses revealed that the VHn to VHa repertoire shift did not occur, demonstrating the requirement for interactions between GALT and intestinal microflora in the selective expansion of VHa B cells. By comparing amino acid sequences of VHn and VHa Ig, we identified a putative VH ligand binding site for a bacterial or endogenous B cell superantigen. We propose that interaction of such a superantigen with VHa B cells results in their selective expansion.

Non-linear connections between dune activity and climate in the High Plains, Kansas and Oklahoma, USA

2011 ◽  
Vol 75 (1) ◽  
pp. 267-277 ◽  
Author(s):  
Corey M. Werner ◽  
Joseph A. Mason ◽  
Paul R. Hanson
Keyword(s):  
Particle Size ◽  
Great Plains ◽  
Water Retention ◽  
Particle Size Analysis ◽  
Size Analysis ◽  
High Plains ◽  
Linear Connections ◽  
The Relationship ◽  
Dune Activity

AbstractDiscrete dune fields are found throughout much of the Great Plains of North America, and the timing of past dune activity is often used as a proxy for paleoclimate because of the intuitive link between dune activity and a more arid climate. This research suggests that feedbacks in the soil-geomorphic system create a relationship between dune activity and climate that varies both spatially and temporally. Older eolian landforms are more resistant to activation because of the long-term accumulation of finer soil particles in a Bt horizon which retain moisture and anchor the deposit even during more arid times. Conversely, younger deposits lack these fines and are more easily reactivated. This spatially variable relationship is supported by soil stratigraphy, particle size analysis, and optical age control. Additionally, the water retention of the Bt horizons is quantifiably greater than that of the soils found in the younger dunes of the area. This complication in the relationship between eolian activity and climate is important because it suggests that caution is needed when using past dune activity as the lone proxy for paleoclimate.

scholarly journals Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen binding affinity

2018 ◽  
Author(s):  
Pia Dosenovic ◽  
Ervin E. Kara ◽  
Anna-Klara Pettersson ◽  
Andrew McGuire ◽  
Matthew Gray ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Neutralizing Antibodies ◽  
Cell Receptor ◽  
Broadly Neutralizing Antibodies ◽  
Precursor Frequency ◽  
The Relationship ◽  
Anti Hiv ◽  
Hiv 1

AbstractThe discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination, and instead that it would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin knock-in mice. Sequential immunization with a series of specifically designed immunogens was required to shepherd the development of bNAbs. However, knock-in mice contain super-physiologic numbers of bNAb precursor expressing B cells and therefore how these results can be translated to a more physiologic setting remains to be determined. Here we make use of adoptive transfer experiments using knock-in B cells that carry a synthetic intermediate in the pathway to anti-HIV-1 bNAb development to examine how the relationship between B cell receptor affinity and precursor frequency affects germinal center B cell recrutiment and clonal expansion. Immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the germinal center when there are as few as 10 such cells per mouse. However, at low precursor frequencies the extent of clonal expansion is directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to germinal centers is variable and dependent on re-circulation.Significance statementAn essential requirement for an HIV-vaccine is to elicit antibodies to conserved regions of the spike protein (Env) becasue these antibodies can protect against infection. Although broadly neutralizing antibodies develop naturally in rare individuals after prolongued HIV infection, eliciting them by vaccination has only been possible in artificial knock-in mouse models wherein the number of B cells expressing the antibody precursor is super-physiologic. To understand the relationship between precursor frequency, antigen affinity and germinal center recruitment we have performed adoptive transfer experiments in which fixed numbers of precursor cells are engrafted in wild type mice. Our results provide a framework for understanding how precursor frequency and antigen affinity shape humoral immunity to HIV.

scholarly journals CpG-activated Regulatory B-cell Progenitors Alleviate Murine Sclerodermatous Chronic GVHD

2021 ◽  
Author(s):  
Viviane A Agbogan ◽  
Pauline Gastineau ◽  
Emmanuel Tejerina ◽  
Saoussen Karray ◽  
Flora Zavala
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Bone Marrow Cells ◽  
Cytokine Expression ◽  
Skin Fibrosis ◽  
Disease Symptoms ◽  
Regulatory B Cell

Abstract BackgroundDevelopment of chronic Graft Versus Host Disease (cGVHD) represents a major impediment in allogeneic hematopoietic stem cell transplantation (HSCT). This disorder is associated with severe impairment of B-cell homeostasis, regulatory B-cell function and distribution. Conversely, the presence of bone marrow and circulating hematogones is associated with reduced GVHD risks. These findings raised the question whether B-cell progenitors, which provide protection in various autoimmune disease models following activation with the TLR-9 agonist CpG (CpG-proBs), could likewise reduce disease symptoms in a sclerodermatous model of cGVHD. MethodsChronic sclerodermatous GVHD was induced in irradiated Balb/c recipients reconstituted with T- and B-cell-depleted bone marrow cells and splenocytes from C57BL/6J donors. CpG-proB-cell progenitors sorted from in vitro CpG-activated bone marrow cells were then adoptively transferred into GVHD recipients. Their effect on disease symptoms, such as diarrhea, skin fibrosis and survival was evaluated in the therapeutic window defined beforehand. Transferred progenitors were analyzed for migration, differentiation and cytokine expression using flow cytofluorimetric methods, which were also used to establish their impact on T-cell cytokine expression and follicular helper/regulatory T-cell ratios (Tfh/Tfr) in peripheral and mesenteric lymph nodes. Skin fibrosis was assessed by histology, identification of infiltrating cells and gene expression profiles of cytokines and molecules involved in the fibrotic process, using qRT-PCR microarrays in all tissue samples.ResultsWe found that CpG-proBs, adoptively transferred during the initial phase of disease, reduced the diarrhea score and mostly prevented cutaneous fibrosis. Progenitors migrated to the draining lymph nodes and to the skin where they mainly differentiated into follicular B cells. CpG activation and IFN-γ expression were required for the protective effect, which resulted in reduced CD4+ T-cell-derived production of cytokines critically involved in cGVHD, such as TGF-β, IL-13 and IL-21. Adoptive transfer increased the Tfr/Tfh ratio. Moreover, CpG-proBs privileged the accumulation of IL-10-positive CD8+ T cells, B cells and dendritic cells in the skin. ConclusionOur findings support the notion that adoptively transferred CpG-proBs provide an efficient strategy for alleviating sclerodermatous cGVHD either per se or as a beneficial adjunct to the HSC graft.

scholarly journals Very Low Affinity B Cells Form Germinal Centers, Become Memory B Cells, and Participate in Secondary Immune Responses When Higher Affinity Competition Is Reduced

2002 ◽  
Vol 195 (9) ◽  
pp. 1215-1221 ◽  
Author(s):  
Joseph M. Dal Porto ◽  
Ann M. Haberman ◽  
Garnett Kelsoe ◽  
Mark J. Shlomchik
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
B Lymphocytes ◽  
Germinal Center ◽  
Germinal Centers ◽  
Association Constants ◽  
Memory B Cells ◽  
B Cell Antigen Receptor ◽  
The Relationship

To understand the relationship between the affinity of the B cell antigen receptor (BCR) and the immune response to antigen, two lines of immunoglobulin H chain transgenic (Tg) mice were created. H50Gμa and T1(V23)μa mice express μ H chain transgenes that associate with the λ1 L chains to bind the (4-hydroxy-3-nitrophenyl)acetyl hapten with association constants (Kas) of only 1.2 × 105 M−1 and 3 × 104 M−1, respectively. Both lines mounted substantial antibody-forming cell (AFC) and germinal center (GC) responses. H50Gμa Tg mice also generated memory B cells. T1(V23)μa B cells formed AFC and GCs, but were largely replaced in late GCs by antigen-specific cells that express endogenous BCRs. Thus, B lymphocytes carrying BCRs with affinities previously thought to be irrelevant in specific immune responses are in fact capable of complete T cell–dependent immune responses when relieved of substantial competition from other B cells. The failure to observe such B cells normally in late primary responses and in memory B cell populations is the result of competition, rather than an intrinsic inability of low affinity B cells.

Monoclonal B-cell lymphocytosis and prostate cancer: incidence and effects of radiotherapy

2019 ◽  
Vol 67 (4) ◽  
pp. 779-782 ◽  
Author(s):  
Fiorella D’Auria ◽  
Luciana Valvano ◽  
Luciana Rago ◽  
Teodora Statuto ◽  
Giovanni Calice ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
B Cells ◽  
B Cell ◽  
Single Case ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Benign Condition ◽  
Healthy Elderly ◽  
The Relationship ◽  
Healthy Elderly People

Monoclonal B-cells lymphocytosis (MBL) is a benign condition that may precede chronic lymphocytic leukemia (CLL), not rarely present in peripheral blood of healthy elderly people, among which there is also a male prevalence. Though CLL has been associated with various types of solid tumors, including prostate cancer (PC), no data exist about the relationship between PC and MBL. We studied the frequency of CLL-like MBL clones in a group of 48 patients affected by PC and followed them during and after whole-pelvis radiotherapy (WPRT) treatment. We found four MBL clones (8.3%), two of which (4.2%) had a B-cell clonal count >1000 cells/µL (‘clinical MBL’). A single case (1.8%) of ‘low-count’ MBL occurred in a control group of 54 healthy males. Notably, normal B-lymphocytes were consistently affected by WPRT, while MBL clones were less radiosensitive. Our results suggest a possible association between ‘clinical’ MBL and PC and show a different impact of the radiation on monoclonal respect to normal B-cells, which could also imply a greater risk of clonal transformation.

B-cell size influences glucose-stimulated insulin secretion

1993 ◽  
Vol 265 (2) ◽  
pp. C358-C364 ◽  
Author(s):  
E. Giordano ◽  
V. Cirulli ◽  
D. Bosco ◽  
D. Rouiller ◽  
P. Halban ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
B Cells ◽  
B Cell ◽  
Cell Size ◽  
Plaque Assay ◽  
Size Analysis ◽  
Glucose Stimulation ◽  
Glucose Stimulated Insulin Secretion ◽  
Two Populations ◽  
Profile Area

To determine whether the heterogeneous B-cell response to glucose is related to a different metabolic handling of this sugar, we have compared rat B-cells differing in their redox response to glucose stimulation. To this end, a population of B-cells showing increased NAD(P)H autofluorescence after a 15-min exposure to 16.7 mM glucose was sorted from a population of B-cells that, under the very same conditions, failed to show detectable changes in basal NADP(H) autofluorescence. Insulin secretion was evaluated by a reverse hemolytic plaque assay in these two populations, referred to as high and low NAD(P)H, respectively. After a 30-min stimulation by 16.7 mM glucose, both populations comprised secreting B-cells and B-cells that did not release detectable amounts of insulin. However, the percentage of secreting B-cells and total insulin output were larger (P < 0.01-0.02) in the high- (77.9 +/- 6.5% and 141.7 +/- 27.4 microns2 x 10(3)) than in the low-NAD(P)H population (58.7 +/- 6% and 92.7 +/- 20.5 microns2 x 10(3)). The high-NAD(P)H population also comprised B-cells that, on average, had a larger (P < 0.001) profile area (142.9 +/- 2.3 microns2) than the B-cells of the low-NAD(P)H population (118.6 +/- 1.5 microns2). Glucose-induced insulin secretion was similar in the high- and low-NAD(P)H group when cells of similar sizes were compared and increased similarly in the two populations as a function of B-cell size. Analysis of variance revealed that insulin secretion was influenced (P < 0.005) by the size of B-cells and not by their NAD(P)H level.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document