1,720,989 research outputs found
CD21–/low B cells in healthy individuals are antigen experienced cells
No full textIn several conditions such as chronic viral infections and primary immunodeficiency, a unique B cell subset has been found expanded. This B cell subset lacks, or expresses low, surface levels of the complement receptor 2 (CD21) and has therefore been termed CD21–/low B cells. However, little is known about the CD21–/low B cell subset in peripheral blood from healthy donors. We show that CD21–/low cells represent approximately 5% of B cells in peripheral blood from adults but are barely detectable in cord blood, after excluding transitional B cells. The CD21–/low subset can be divided into CD38– 24+ and CD38– 24low cells, where most of the CD38– 24+ are CD27+ IgM+ IgD+ and the CD38– 24low are switched CD27–. Expression levels of additional markers, e.g. CD95 and CD62L, are similar to those on classical memory B cells. The majority of CD21–/low cells lack expression of the ABCB1 transporter, which is a marker restricted to naïve B cells. We also investigated the CD21–/low B cells response to various single stimuli. In order to do that, we determined the change in CD69 expression, an activation marker, after 3 hours stimulation. Both CD21+ naïve and memory B cells responded to all single stimuli by up-regulation of CD69 and to a similar extent. The CD21–/low subsets did not respond to the same extent and the lowest response was observed for the CD24low subset. Stimulation with a combination of BCR, Toll-like receptor (TLR) 7/8 and interleukin (IL)2 induces proliferation and differentiation of the CD21–/low B cells comparable to CD21+CD27+ memory B cells. Their response excluding BCR agonist is not on par with that of classical memory B cells, although clearly above that of naïve B cells. In conclusion, as in disease and tonsils of healthy individuals, the CD21–/low B cell subset in peripheral blood from healthy adults is a functionally and phenotypically heterogeneous population composed mainly of memory B cells
CD21-/low B cells: a snapshot of a unique B cell subset in health and disease
Full text linkB cells represent one of the cellular components of the immune system thatprotects the individual from invading pathogens. In response to the invader,these cells differentiate into plasma cells and produce large amounts of antibodiesthat bind to and eliminate the pathogen. A hallmark of autoimmune diseases isthe production of autoantibodies i.e. antibodies that recognize self. Those that areconsidered pathogenic can damage tissues and organs, either by direct binding orwhen deposited as immune complexes. For decades, B cells have been consideredto play a major role in autoimmune diseases by antibody production. However, aspathogenic autoantibodies appear to derive mainly from T cell dependentresponses, T cells have been the focus for many years. The successful treatment ofpatients with autoimmune diseases with either B cell depletion therapy(rituximab) or inhibition of B cell survival (belimumab), suggested that notonly the autoantibodies but also other B cell features are important. This hascaused a surg e of interest in B cells and their biology resulting in theidentification of various subsets e.g. regulatory B cells, several memory B cellsubsets etc. Also, in other conditions such as chronic viral infect ions and primaryimmunodeficiency, several B cell subsets with unique characteristics have beenidentified. In this review, we will discuss one of these subsets, a subset that isexpanded in conditions characterized by chronic immune stimulation. This B cellsubset lacks, or expresses low, surface levels of the complement receptor 2(CD21) and has therefore been termed CD21-/lowB cell
Intravenous immunoglobulin replacement therapy in common variable immunodeficiency induces B cell depletion through differentiation into apoptosis-prone CD21low B cells
No full textntravenous immunoglobulin (IVIG), besides its use as replacement therapy in patients with antibody defi- ciencies, is broadly used as an immunomodulatory agent for the treatment of autoimmune and inflammatory disorders. The mechanisms of action of IVIG include Fc receptor blockade, inhibition of cytokines and growth factors, modulation of macrophages and dendritic cells, enhancement of regulatory T cells, and modulation of B cells through the FccRIIB receptor and CD22. Recent studies suggest that in vitro exposure of human B cells to IVIG determines functional changes reminiscent of anergy and that IVIG treatment of patients with common variable immunodeficiency (CVID) induces in B cells ERK activation, a feature of anergy. Here, we show that IVIG therapy drives the B cells of patients with CVID to down-regulate CD21 expression and to assume the peculiar phenotype of the anergic-like, apoptosis-prone CD21low B cells that are spontaneously expanded in a subset of CVID and in some other immunological disorders. The CD21low B cells newly generated after IVIG infusion undergo spontaneous apoptosis upon in vitro culture. Furthermore, IVIG infusion is rapidly followed by a significant, although discrete, decrease in the number of circulating B cells, but not of T cells or of natural killer cells. These findings suggest that IVIG therapy may constrain antibody responses by inducing B cell depletion through differentiation into CD21low B cells that undergo accelerated apoptosis
Immunomodulatory effects of intravenous immunoglobulin - assembling a jigsaw puzzle
No full textIntravenous immunoglobulin (IVIG) is widely used for the treatment of autoimmune and inflammatory disorders because of its immunomodulatory effects. The interaction of IVIG with the immune system has been extensively investigated over the past 30 years but, since IVIG modifies responses of many immune cells, a unifying model is far from reach. Here we survey the in vitro studies on the effects on IVIG on macrophages, B cells, T regulatory cells, dendritic cells and soluble factors, as well as the in vivo studies in murine disease models and the preliminary in vivo findings in humans
Dysregulated extracellular signal-regulated kinase signaling associated with impaired B-cell receptor endocytosis in patients with common variable immunodeficiency
No full textBACKGROUND:
Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by B-cell dysfunction and, in a subgroup, by expansion of CD21(low) B cells. The CD21(low) B cells display defects in early B-cell receptor (BCR) signaling resembling those of anergic B cells.
OBJECTIVE:
We sought to investigate whether B cells from patients with CVID, like anergic B cells, have defects in extracellular signal-regulated kinase (ERK) phosphorylation and in endocytic trafficking of the BCR.
METHODS:
Using flow cytometry, we evaluated phosphorylated ERK (pERK) expression and internalization of cross-linked BCR in B-cell subsets. The localization of internalized BCR to lysosome-associated membrane protein 1-positive late endosomes was evaluated with confocal microscopy.
RESULTS:
Constitutive pERK levels were increased in naive and IgM(+) memory B cells of patients with CVID compared with those of healthy donors, whereas the pERK increment induced by BCR cross-linking was relatively reduced. Intravenous immunoglobulin administration enhanced these anomalies, but they appeared to be intrinsic to B cells from patients with CVID. Cross-linking-induced BCR endocytosis was decreased in the IgM(+) memory B cells, especially in those with a CD21(low) phenotype, but not in the naive B cells of patients with CVID with CD21(low) expansion. Internalized BCR localized normally to late endosomes. Pharmacologic inhibition of ERK phosphorylation suppressed BCR endocytosis in B cells of healthy patients and those with CVID.
CONCLUSIONS:
The B cells of patients with CVID with CD21(low) B-cell expansion resemble anergic B cells based on high constitutive pERK expression. The IgM(+) memory B cells of these patients, especially those that are CD21(low), have a defect in BCR endocytosis seemingly caused by dysregulated ERK signalin
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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