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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
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
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
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
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
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
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
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
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 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
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
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,
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
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
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
This guide is designed to be a simple introduction to the challenge of doing a grounded theory with online sources. A significant number of social settings are now online, and it is important to have effective ways of studying those settings. The guide gives a brief primer into the four key issues of grounded theory as a methodology for online studies. First, the guide discusses the background of
Conventional dialyzer membranes typically comprise of unevenly distributed polydisperse, tortuous, rough pores, embedded in relatively thick ≈20–50 µm polymer layers wherein separation occurs via size exclusion as well as differences in diffusivity of the permeating species. However, transport in such polymeric pores is increasingly hindered as the molecule size approaches the pore dimension, resu
