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Conserved sequence elements in K promoters from mice and humans : Implications for transcriptional regulation and repertoire expression

Promoter region sequences of human and mouse Igk-V genes were aligned and found to be conserved for about 200-300 base pairs (bp) within subgroups/families. No promoter similarity was found between IGKV promoters from different human subgroups. Related mouse Igk-V gene families were conserved in the promoter region but no similarity was evident when promoters from unrelated Igk-V gene families wer

Expression of the chemokine decoy receptor D6 is decreased in colon adenocarcinomas

Recruitment of immune cells to tumors is a complex process crucial for both inflammation-driven tumor progression and specific anti-tumor cytotoxicity. Chemokines control the directed migration of immune cells, and their actions are partly controlled by nonsignaling chemokine decoy receptors. The role of the receptors such as D6, Duffy antigen receptor for chemokines and ChemoCentryx chemokine rec

Class-switch recombination to IgA in the Peyer’s patches requires natural thymus-derived Tregs and appears to be antigen independent

Our understanding of how class-switch recombination (CSR) to IgA occurs in the gut is still incomplete. Earlier studies have indicated that Tregs are important for IgA CSR and these cells were thought to transform into follicular helper T cells (Tfh), responsible for germinal center formation in the Peyer’s patches (PP). Following adoptive transfer of T-cell receptor-transgenic (TCR-Tg) CD4 T cell

Determination of blood cell subtype concentrations from frozen whole blood samples using TruCount beads

Background: In many studies it would be advantageous if blood samples could be collected and analyzed using flow cytometry at a later stage. Ideally, sample collection should involve little hands-on time, allow for long-term storage, and minimally influence the samples. Methods: Here we establish a flow cytometry antibody panel that can be used to determine granulocytes, monocytes, and lymphocyte

Making inventory : Mapping and Exploring Zimbabwe Sites

Inspired by the work of Paul Sinclair we yearn for the publication of a guidebook to provide an inventory of Zimbabwe Sites (Sinclair 1987, 1989, 1993, 2010). These sites are the tangible archaeological espression and hence vital evidence of the anatomy of the precolo-nial state in Zimbabwe (Pikirayi 1993, 2001; Pwiti 1996, Mudenge 2011, Beach 1980). The precolonial history of Zimbabwe may be rend

Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses

Whereas gut IgA responses to the microbiota may be multi-centered and diverse, little is known about IgA responses to T-cell-dependent antigens following oral immunizations. Using a novel approach, gut IgA responses to oral hapten (4-hydroxy-3-nitrophenyl)acetyl-cholera toxin (NP-CT) conjugates were followed at the cellular and molecular level. Surprisingly, these responses were highly synchronize

Somatic hypermutation in the absence of DNA-dependent protein kinase catalytic subunit (DNA-PK(cs)) or recombination-activating gene (RAG)1 activity

Somatic hypermutation and isotype switch recombination occur in germinal center B cells, are linked to transcription, and are similarly affected by deficiency in MutS homologue (MSH)2. Class-switch recombination is abrogated by disruption of genes encoding components of the catalytic subunit of DNA-dependent protein kinase (DNA-PK(cs))/Ku complex and likely involves nonhomologous end joining (NHEJ

Know your enemy or find your friend?—Induction of IgA at mucosal surfaces

Most antibodies produced in the body are of the IgA class. The dominant cell population producing them are plasma cells within the lamina propria of the gastrointestinal tract, but many IgA-producing cells are also found in the airways, within mammary tissues, the urogenital tract and inside the bone marrow. Most IgA antibodies are transported into the lumen by epithelial cells as part of the muco

Spi-C, a novel Ets protein that is temporally regulated during B lymphocyte development

A novel Ets protein was isolated by yeast one-hybrid screening of a cDNA library made from lipopolysaccharide-stimulated mouse splenic B cells, using the SP6 κ promoter κY element as a bait. The novel Ets protein was most closely related to PU.1 and Spi-B within the DNA binding Ets domain and was therefore named Spi-C. However, Spi-C may represent a novel subgroup within the Ets protein family, as

Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells

Neuroblastoma is the most commonly diagnosed extracranial tumor in the first year of life. Approximately 9% of neuroblastoma patients present germline or somatic aberrations in the gene encoding for anaplastic lymphoma kinase (ALK). This increases in high-risk neuroblastomas, which have a 14% frequency of ALK aberrations at the time of diagnosis and show increasing numbers at relapse. Abrogating A

Translational Mini-Review Series on B cell subsets in disease. Reconstitution after haematopoietic stem cell transplantation - revelation of B cell developmental pathways and lineage phenotypes

Haematopoietic stem cell transplantation (HSCT) is an immunological treatment that has been used for more than 40 years to cure a variety of diseases. The procedure is associated with serious side effects, due to the severe impairment of the immune system induced by the treatment. After a conditioning regimen with high-dose chemotherapy, sometimes in combination with total body irradiation, haemat

Promotion of immunoglobulin gene transcription

In this article, Mats Bemark and Tomas Leanderson discuss the levels at which immunoglobulin gene transcription is controlled, and highlight the complex nature and mode of action of immunoglobulin promoters.

Murine germinal center B cells require functional fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination

Switched antibody classes are important for efficient immune responses. Aberrant antibody production to otherwise harmless antigens may result in autoimmunity. The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before. Herein we describe a previously unappreciated role

The composition of the gut microbiota shapes the colon mucus barrier

Two C57BL/6 mice colonies maintained in two rooms of the same specific pathogen-free (SPF) facility were found to have different gut microbiota and a mucus phenotype that was specific for each colony. The thickness and growth of the colon mucus were similar in the two colonies. However, one colony had mucus that was impenetrable to bacteria or beads the size of bacteria - which is comparable to wh

T cell-independent IgA class switch recombination is restricted to the GALT and occurs prior to manifest germinal center formation

Recently, we reported that CD40-/- mice, exhibiting exclusively T cell-independent IgA class switch recombination (CSR), demonstrated near normal levels of IgA plasma cells in the gut lamina propria (LP), despite the complete lack of germinal centers (GCs). In this study, we have extended our analysis focusing on how to reconcile these findings using flow cytometry and molecular markers for IgA CS

BCR affinity differentially regulates colonization of the subepithelial dome and infiltration into germinal centers within Peyer’s patches

Gut-derived antigens trigger immunoglobulin A (IgA) immune responses that are initiated by cognate B cells in Peyer’s patches (PPs). These cells colonize the subepithelial domes (SEDs) of the PPs and subsequently infiltrate pre-existing germinal centers (GCs). Here we defined the pre-GC events and the micro-anatomical site at which affinity-based B cell selection occurred in PPs. Using whole-organ

Differentiation-specific, octamer-dependent costimulation of κ transcription

By mutational analysis of the octamer-TATA box intervening region in the mouse SP6 κ promoter, we have mapped two octamer-dependent, costimulatory regions, A and B. The A region was active in late B cells only, while the B region was active throughout B cell differentiation. The B region was TATA proximal and contained a heptamer and an E box of the E2A type that is common in Vκ promoters. Mutatio

Gut IgA class switch recombination in the absence of CD40 does not occur in the lamina propria and is independent of germinal centers

Conflicting findings have recently been presented as to the sites and sources of B cells that undergo class switch recombination (CSR) to IgA in the gut. In this study we provide compelling evidence in CD40-/- mice demonstrating that IgA CSR can be independent of CD40 signaling and germinal center formation and does not occur in the gut lamina propria (LP) itself. We found that CD40-/- mice had ne

Mucosal adjuvants and long-term memory development with special focus on CTA1-DD and other ADP-ribosylating toxins

The ultimate goal for vaccination is to stimulate protective immunological memory. Protection against infectious diseases not only relies on the magnitude of the humoral immune response, but more importantly on the quality and longevity of it. Adjuvants are critical components of most non-living vaccines. Although little attention has been given to qualitative aspects of the choice of vaccine adju

Single-cell atlas reveals meningeal leukocyte heterogeneity in the developing mouse brain

The meninges are important for brain development and pathology. Using single-cell RNA sequencing, we have generated the first comprehensive transcriptional atlas of neonatal mouse meningeal leukocytes under normal conditions and after perinatal brain injury. Weidentified almost all known leukocyte subtypes and found differences between neonatal and adult border-associated macrophages, thus highlig