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Epstein-barr virus, but not cytomegalovirus, latency accelerates the decay of childhood measles and rubella vaccine responses-A 10-year follow-up of a Swedish birth cohort

Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are ubiquitous and persistent herpesviruses commonly acquired during childhood. Both viruses have a significant impact on the immune system, especially through mediating the establishment of cellular immunity, which keeps these viruses under control for life. Far less is known about how these viruses influence B-cell responses. Objecti

In vivo and in vitro studies of immunoglobulin gene somatic hypermutation

Following antigen encounter, two distinct processes modify immunoglobulin genes. The variable region is diversified by somatic hypermutation while the constant region may be changed by class-switch recombination. Although both genetic events can occur concurrently within germinal centre B cells, there are examples of each occurring independently of the other. Here we compare the contributions of c

Human marginal zone B cell development from early T2 progenitors

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch

By-products of immunoglobulin somatic hypermutation

The antigen receptor loci are the only loci in humans to undergo programmed somatic gene modification. Although aberrant V(D)J integration and class switch recombination can both give rise to chromosomal translocations, a role for somatic hypermutation in such genomic rearrangements has been suggested but is less clearly established. To characterize the types of by-products of somatic hypermutatio

Purification and characterization of a protein binding to the SP6 κ promoter : A potential role for CArG-box binding factor-A in κ transcription

A protein interacting with an A-T-rich region that is a positive control element within the SP6 κ promoter was purified and identified as CArG-box binding factor-A. The purified protein was shown to interact specifically with the coding strand of single-stranded DNA and, with lower affinity, with double-stranded DNA. A mutation that inhibited binding of the protein to the A-T-rich region also abor

Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue

Human memory B cells and marginal zone (MZ) B cells share common features such as the expression of CD27 and somatic mutations in their IGHV and BCL6 genes, but the relationship between them is controversial. Here, we show phenotypic progression within lymphoid tissues as MZ B cells emerge from the mature naïve B cell pool via a precursor CD27−CD45RBMEM55+ population distant from memory cells. By

Identification of genes deregulated during serum-free medium adaptation of a Burkitt's lymphoma cell line

Objective: Serum is usually added to growth media when mammalian cells are cultured in vitro to supply the cells with growth factors, hormones, nutrients and trace elements. Defined proteins and metal ions, such as insulin, growth factors, transferrin and sodium selenite, are sometimes also included and can in some cases substitute serum components. How adaptation to serum free media influences ce

The c-MYC allele that is translocated into the IgH locus undergoes constitutive hypermutation in a Burkitt's lymphoma line

Burkitt's lymphomas harbour chromosomal translocations bringing c-MYC into the vicinity of one of the immunoglobulin gene loci. Point mutations have been described within c-MYC in several Burkitt's lymphomas and it has been proposed that translocation into the Ig loci might have transformed c-MYC into a substrate for the antibody hypermutation mechanism. Here we test this hypothesis by exploiting

Molecular view of ER membrane remodeling by the Sec61/TRAP translocon

Protein translocation across the endoplasmic reticulum (ER) membrane is an essential step during protein entry into the secretory pathway. The conserved Sec61 protein-conducting channel facilitates polypeptide translocation and coordinates cotranslational polypeptide-processing events. In cells, the majority of Sec61 is stably associated with a heterotetrameric membrane protein complex, the transl

Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization

Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with chole

The regulation of gut mucosal IgA B-cell responses : Recent developments

The majority of activated B cells differentiate into IgA plasma cells, with the gut being the largest producer of immunoglobulin in the body. Secretory IgA antibodies have numerous critical functions of which protection against infections and the role for establishing a healthy microbiota appear most important. Expanding our knowledge of the regulation of IgA B-cell responses and how effective muc

An Ultrahigh‐Density Microneedle Array for Skin Vaccination: Inducing Epidermal Cell Death by Increasing Microneedle Density Enhances Total IgG and IgG1 Immune Responses

Many types of microneedle (MN) arrays have been tested for delivery of vaccines to the skin. However, the effect of MN geometry/array design on antibody production is still unclear. Reports suggest that systemic immune responses may be affected by how MN arrays “mechanically” deliver vaccines, which can induce cell damage and act as an adjuvant. This includes parameters such as MN length/insertion

Nu krävs satsning på forskning för ett hållbart arbetsliv

Debatt: Vi vill att forskningsråden skapar tvärvetenskapliga regionala forskningscentrum för arbetslivsforskning, som är internationellt konkurrenskraftiga och ger nationellt och regionalt kunskapsstöd. Dessa centrum ska ge kunskaper för både befintliga och framtida utmaningar. Stora vinster kan fås om forskning om folkhälsa och yttre miljö samordnas i centrumen. Arbetslivet är grunden för hälsa,

Rooting out the root causes of order fulfilment errors : a multiple case study

While recent technological advancements have enabled improved performance in warehouse operations, companies still struggle with eliminating errors such as incorrect/damaged items or the wrong quantity sent to customers. Such errors result in inefficient resource use, costly returns handling, and customer dissatisfaction. Despite the importance of errors, current knowledge of the underlying causes

Sociodemographic characteristics and COVID-19 testing rates : spatiotemporal patterns and impact of test accessibility in Sweden

BACKGROUND: Diagnostic testing is essential for disease surveillance and test-trace-isolate efforts. We aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with Coronavirus Disease 2019 (COVID-19) testing rates.METHODS: We included 426 224 patient-initiated COVID-19 polymerase chain reaction tests from Uppsala County in Sweden from 24 Ju

Opioid dispensing in relation to arthroscopic knee surgery in Denmark from 2006 to 2018

INTRODUCTION. In the US, opioids are commonly prescribed after arthroscopic knee surgery. We aimed to investigate opioid dispensing in relation to arthroscopic knee surgeries from 2006 to 2018 in Denmark. METHODS. In Danish registries, we identified patients (≥ 15 years old) having arthroscopic knee surgery (anterior cruciate ligament (ACL) reconstruction; meniscal surgery; cartilage resection; sy