Dataset Information

Decreased IL7R? and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin.

ABSTRACT: Newborns are unable to mount antibody responses towards certain antigens. This has been related to the restricted repertoire of immunoglobulin (Ig) genes of their B cells. The mechanisms underlying the restricted fetal Ig gene repertoire are currently unresolved. We here addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. In the absence of selection processes, fetal B-cell progenitors more frequently used proximal V, D and J genes in complete IGH gene rearrangements, despite normal Ig locus contraction. Fewer N-nucleotides were added in IGH gene rearrangements in the context of low TdT and XRCC4 expression. Moreover, fetal progenitor-B cells expressed lower levels of IL7R? than their pediatric counterparts. Analysis of progenitor-B cells from IL7R?-deficient patients revealed that TdT expression and N-nucleotides additions in Dh-Jh junctions were dependent on functional IL7R?. Thus, IL7R? affects TdT expression, and decreased expression of this receptor underlies at least in part the skewed Ig repertoire formation in fetal B-cell precursors. These new insights provide a better understanding of the formation of adaptive immunity in the developing fetus.

SUBMITTER: Rother MB

PROVIDER: S-EPMC5034271 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Decreased IL7Rα and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin.

Rother Magdalena B MB Jensen Kristin K van der Burg Mirjam M van de Bovenkamp Fleur S FS Kroek Roel R van IJcken Wilfred F J WF van der Velden Vincent H J VH Cupedo Tom T Olstad Ole K OK van Dongen Jacques J M JJ van Zelm Menno C MC

Scientific reports 20160923

Newborns are unable to mount antibody responses towards certain antigens. This has been related to the restricted repertoire of immunoglobulin (Ig) genes of their B cells. The mechanisms underlying the restricted fetal Ig gene repertoire are currently unresolved. We here addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. In the absence of selection processes, fetal B-cell progenitors more frequently ...[more]

PMID: 27658954

Similar Datasets

Project description:ObjectivesThe overall goal of the study was to identify functional and behavioral differences between individuals with higher tinnitus distress and individuals with lower tinnitus distress. Subsequent exploratory analyses were conducted to investigate the role physical activity may have on the observed results between high and low distress groups. The purpose of the experiment was to identify brain regions to be targeted in future intervention studies for tinnitus.DesignA total of 32 individuals with varying levels of tinnitus severity were recruited from the Urbana-Champaign area. Volunteers were divided into higher tinnitus distress (HD) and lower tinnitus distress (LD) groups. Note that these groups also significantly differed based on physical activity level and were subsequently stratified into higher and lower physical activity level subgroups for exploratory analysis. While in a functional magnetic resonance imaging (fMRI) scanner, subjects listened to affective sounds classified as pleasant, neutral or unpleasant from the International Affective Digital Sounds database.ResultsThe HD group recruited amygdala and parahippocampus to a greater extent than the LD group when listening to affective sounds. The LD group engaged frontal regions to a greater extent when listening to the affective stimuli compared to the HD group. Both higher physical activity level subgroups recruited more frontal regions, and both lower levels of physical activity subgroups recruited more limbic regions respectively.ConclusionIndividuals with lower tinnitus distress may utilize frontal regions to better control their emotional response to affective sounds. Our analysis also suggests physical activity may contribute to lower tinnitus severity and greater engagement of the frontal cortices. We suggest that future intervention studies focus on changes in the function of limbic and frontal regions when evaluating the efficacy of treatment. Additionally, we recommend further investigation concerning the impact of physical activity level on tinnitus distress.

Project description:Adequate maternal nutrition during gestation is requisite for fetal nutrition and development. While a large group of epidemiological studies indicate poor fetal nutrition increases heart disease risk and mortality in later life, little work has focused on the effects of impaired maternal nutrition on fetal heart development. We have previously shown that 50% global nutrient restriction from 28-78 days of gestation (early to mid-pregnancy; term = 147 days) in sheep at mid-gestation retards fetal growth while protecting growth of heart and results in hypertensive male offspring at nine months of age. In the present study, we evaluate LV gene transcription using RNA protection assay and real-time reverse transcriptase polymerase chain reaction, and protein expression using western blot, of VEGF and AT1 and AT2 receptors for AngII at mid-gestation in fetuses from pregnant ewes fed either 100% (C) or 50% (NR) diet during early to mid-gestation.No difference between the NR (n = 6) and C (n = 6) groups was found in gene transcription of the AngII receptors. Immunoreactive AT1 (1918.4 +/- 154.2 vs. 3881.2 +/- 494.9; P < 0.01) and AT2 (1729.9 +/- 293.6 vs. 3043.3 +/- 373.2; P < 0.02) was decreased in the LV of NR fetuses compared to C fetuses. The LV of fetuses exposed to NR had greater transcription of mRNA for VEGF (5.42 +/- 0.85 vs. 3.05 +/- 0.19; P < 0.03) than respective C LV, while no change was observed in immunoreactive VEGF.The present study demonstrates that VEGF, AT1 and AT2 message and protein are not tightly coupled, pointing to post-transcriptional control points in the mid gestation NR fetus. The present data also suggest that the role of VEGF and the renin-angiotensin system receptors during conditions inducing protected cardiac growth is distinct from the role these proteins may play in normal fetal cardiac growth. The present findings may help explain epidemiological studies that indicate fetuses with low birth weight carry an increased risk of mortality from coronary and cardiovascular disease, particularly if these individuals have reduced cardiovascular reserve due to an epigenetic decrease in vascularization.

Dataset Information

Decreased IL7R? and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin.

Publications

Decreased IL7Rα and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure