UNASSIGNED: Infection is an important cause of morbidity in children with sickle cell anaemia (SCA). However, little is currently known regarding the spectrum of adaptive immune derangement in SCA, especially of populations in Sub-Saharan Africa. In this study, we investigated the phenotype and activation status of T and B lymphocytes among children with SCA in Tanzania.
UNASSIGNED: We compared 30 children with SCA aged 1-6 years in steady-state with 10 age-matched controls. We assessed white blood cell count, T and B lymphocyte phenotype and activation status using an automated haematology analyser and multiparameter Flow Cytometry.
UNASSIGNED: In children with SCA, the absolute lymphocyte, monocyte and granulocyte counts were all increased. There was also an increase in proportion of central/transitional memory (42.4% vs. 33.3%, p = 0.0100), effector memory (7.8% vs. 5.4%, p = 0.0086) and terminally differentiated (2.3% vs. 1.3%, p = 0.0355) CD4+ T cells as well as effector memory CD8+ T cells (21.3% vs. 11.5%, p = 0.0060) in children with SCA. In contrast, there was no difference in naïve, classical memory, atypical memory and IgM memory B-cells between the two groups. The level of activation of both T and B cells were comparable between children with and without SCA. Furthermore, we observed a significant inverse correlation between frequency of the effector memory CD8+ T cells and haematocrit (Spearman rho = -0.3859, p = 0.0352).
UNASSIGNED: Children with SCA in Tanzania show an absolute increase in all leukocyte types, including lymphocytes, with skewing of both CD4+ and CD8+ T cells towards the memory phenotypes. These findings provide insights on the development of adaptive immunity which may have implications on vaccine responsiveness, allo-immunisation, auto-immune diseases and transplant immunology in children with SCA.

UNASSIGNED: In systemic sclerosis (SSc), B-cells are activated and present in the skin and lung of patients where they can interact with fibroblasts. The precise impact and mechanisms of the interaction of B-cells and fibroblasts at the tissular level are poorly studied.
UNASSIGNED: We investigated the impact and mechanisms of B-cell/fibroblast interactions in cocultures between B-cells from patients with SSc and 3-dimensional reconstituted healthy skin model including fibroblasts, keratinocytes and extracellular matrix.
UNASSIGNED: The quantification and description of the B-cell infiltration in 3D cocultures were performed using cells imagery strategy and cytometry. The effect of coculture on the transcriptome of B-cells and fibroblasts was studied with bulk and single-cell RNA sequencing approaches. The mechanisms of this interaction were studied by blocking key cytokines like IL-6 and TNF.
UNASSIGNED: We showed a significant infiltration of B-cells in the 3D healthy skin model. The amount but not the depth of infiltration was higher with B-cells from SSc patients and with activated B-cells. B-cell infiltrates were mainly composed of naïve and memory cells, whose frequencies differed depending on B-cells origin and activation state: infiltrated B-cells from patients with SSc showed an activated profile and an overexpression of immunoglobulin genes compared to circulating B-cells before infiltration. Our study has shown for the first time that activated B-cells modified the transcriptomic profile of both healthy and SSc fibroblasts, toward a pro-inflammatory (TNF and IL-17 signaling) and interferon profile, with a key role of the TNF pathway.
UNASSIGNED: B-cells and 3D skin cocultures allowed the modelization of B-cells infiltration in tissues observed in SSc, uncovering an influence of the underlying disease and the activation state of B-cells. We showed a pro-inflammatory effect on skin fibroblasts and pro-activation effect on infiltrating B-cells during coculture. This reinforces the role of B-cells in SSc and provide potential targets for future therapeutic approach in this disease.

Epstein-Barr virus (EBV) is a highly prevalent virus among adults worldwide. In an immunocompetent individual, EBV infection generally results in lifelong latency of the virus and no sequelae. However, in the setting of immune dysfunction, EBV can induce the development of autoimmune disorders, hyperplastic proliferations, and cancers, including lymphoma. Here, we explore the pathogenic and oncogenic role of EBV in Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, plasmablastic lymphoma, lymphomatoid granulomatosis, and post-transplant lymphoproliferative disorders and lymphoproliferative disorders associated with immune deficiency and dysregulation. In addition to describing general mechanisms of EBV-associated oncogenesis, we also discuss EBV-associated oncogenesis in the context of each disorder, as well as their microscopic, phenotypic, and clinical presentations.

B-cell epitope mapping is an approach that can identify and characterise specific antigen binding sites of B-cell receptors and secreted antibodies. The ability to determine the antigenic clusters of amino acids bound by B-cell clones provides unprecedented detail that will aid in developing novel and effective vaccine targets and therapeutic antibodies for various diseases. Here, we discuss conventional approaches and emerging techniques that are used to map B-cell epitopes.

BACKGROUND: Gastric lymphoma is an extremely rare disease in children; it is usually presented with non-specific symptoms, which makes the diagnosis relatively late in most cases. Here we present a case of a primary lymphoblastic B-cell lymphoma of the stomach in a child.
METHODS: A 14 -year- old female presented with abdominal discomfort for three months. On examination, she had a mobile epigastric mass. The CT abdomen showed a mass occupying the lesser curvature of the stomach, which was confirmed by the endoscopy. A subtotal gastrectomy was carried out. Histopathology and flow cytometry for the specimen, along with bone marrow examination confirmed the diagnosis of primary B-cell lymphoblastic gastric lymphoma.
CONCLUSIONS: Primary gastric lymphoma, in particular, is a very rare gastric neoplasm. Furthermore, most of the reported cases are mature B-cell lymphoma subtypes. The clinical presentation in children is the same as for other types of primary gastric malignancies. Moreover, no guidelines are available for the management of such conditions in the paediatric age group. In our case, a surgical resection was carried out; as the initial endoscopic biopsy was suspicious for adenocarcinoma, further workup confirmed the diagnosis of primary lymphoblastic B-cell lymphoma of the stomach.
CONCLUSIONS: Early detection of gastric malignancies in children is a key element in the prognosis. In addition, optimal surgical resection showed a very good outcome.

ETS proto-oncogene 1 (ETS1) is a transcription factor (TF) critically involved in lymphoid cell development and function. ETS1 expression is tightly regulated throughout differentiation and activation in T-cells, natural killer (NK) cells, and B-cells. It has also been described as an oncogene in a range of solid and hematologic cancer types. Among hematologic malignancies, its role has been best studied in T-cell acute lymphoblastic leukemia (T-ALL), adult T-cell leukemia/lymphoma (ATLL), and diffuse large B-cell lymphoma (DLBCL). Aberrant expression of ETS1 in these malignancies is driven primarily by chromosomal amplification and enhancer-driven transcriptional regulation, promoting the ETS1 transcriptional program. ETS1 also facilitates aberrantly expressed or activated transcriptional complexes to drive oncogenic pathways. Collectively, ETS1 functions to regulate cell growth, differentiation, signaling, response to stimuli, and viral interactions in these malignancies. A tumor suppressor role has also been indicated for ETS1 in select lymphoma types, emphasizing the importance of cellular context in ETS1 function. Research is ongoing to further characterize the clinical implications of ETS1 dysregulation in hematologic malignancies, to further resolve binding complexes and transcriptional targets, and to identify effective therapeutic targeting approaches.

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BACKGROUND: It is known that the immune system is dysregulated in schizophrenia, having a state similar to chronic neuroinflammation. The origin of this process is unknown, but it is known that T and B lymphocytes, which are components of the adaptive immune system, play an important role in the pathogenic mechanisms of schizophrenia.
METHODS: We analysed the membrane of PBMCs from patients diagnosed with schizophrenia through proteomic analysis (n = 5 schizophrenia and n = 5 control). We found the presence of the Kv1.3 voltage-gated potassium channel and its auxiliary subunit β1 (KCNAB1) and β2 (KCNAB2). From a sample of 90 participants, we carried out a study on lymphocytes with whole-cell patch-clamp experiments (n = 7 schizophrenia and n = 5 control), western blot (n = 40 schizophrenia and n = 40 control) and confocal microscopy to evaluate the presence and function of different channels. Kv in both cells.
RESULTS: We demonstrated the overexpression of Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3 and Kv7.2 channels in PBMCs from patients with schizophrenia. This study represents a groundbreaking exploration, as it involves an electrophysiological analysis performed on T and B lymphocytes from patients diagnosed of schizophrenia compared to healthy participants. We observed that B lymphocytes exhibited an increase in output current along with greater peak current amplitude and voltage conductance curves among patients with schizophrenia compared with healthy controls.
CONCLUSIONS: This study showed the importance of the B lymphocyte in schizophrenia. We know that the immune system is altered in schizophrenia, but the physiological mechanisms of this system are not very well known. We suggest that the B lymphocyte may be relevant in the pathophysiology of schizophrenia and that it should be investigated in more depth, opening a new field of knowledge and possibilities for new treatments combining antipsychotics and immunomodulators. The limitation is that all participants received antipsychotic medication, which may have influenced the differences observed between patients and controls. This implies that more studies need to be done where the groups can be separated according to the antipsychotic drug.

The genomic analyses of pediatric acute lymphoblastic leukemia (ALL) subtypes, particularly T-cell and B-cell lineages, have been pivotal in identifying potential therapeutic targets. Typical genomic analyses have directed attention toward the most commonly mutated genes. However, assessing the contribution of mutations to cancer phenotypes is crucial. Therefore, we estimated the cancer effects (scaled selection coefficients) for somatic substitutions in T-cell and B-cell cohorts, revealing key insights into mutation contributions. Cancer effects for well-known, frequently mutated genes like NRAS and KRAS in B-ALL were high, which underscores their importance as therapeutic targets. However, less frequently mutated genes IL7R, XBP1, and TOX also demonstrated high cancer effects, suggesting pivotal roles in the development of leukemia when present. In T-ALL, KRAS and NRAS are less frequently mutated than in B-ALL. However, their cancer effects when present are high in both subtypes. Mutations in PIK3R1 and RPL10 were not at high prevalence, yet exhibited some of the highest cancer effects in individual T-cell ALL patients. Even CDKN2A, with a low prevalence and relatively modest cancer effect, is potentially highly relevant for the epistatic effects that its mutated form exerts on other mutations. Prioritizing investigation into these moderately frequent but potentially high-impact targets not only presents novel personalized therapeutic opportunities but also enhances the understanding of disease mechanisms and advances precision therapeutics for pediatric ALL.