The uniqueness of each BCR and width of the B cell repertoire are due to the DNA rearrangements at HC and LC loci. B cells leave the bone marrow at the transitional stage carrying a wide array of germline-encoded and randomly assembled Ig genes. Transitional B cells migrate with the blood to the spleen. They are not fully functional in the immune responses: they are not able to respond to inflammatory chemokines, and engagement of the BCR leads to their apoptotic cell death. These are safety measures against autoreactivity preventing self-reactive transitional B cells from further development and migration to sites rich in cytokines and stimulatory cells. In contrast to the mortal effect of BCR cross-linking, engagement of TLR9 leads to differentiation of transitional B cells. In response to CpG, a fraction of the transitional B cells (26%) proliferates and acquires the phenotype of memory B cells or directly matures into plasma cells. The remaining cells start to express the markers of ...

Martin, VG, Wu, Y-CB, Townsend, CL, Lu, GH, OHare, JS, Mozeika, A, Coolen, AC, Kipling, D, Fraternali, F and Dunn-Walters, Deborah (2016) Transitional B cells in early human B cell development - time to revisit the paradigm? ...

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Using a selection-based cDNA library screen, we identified the cytokine receptor subunit CRLF2 as a factor in poor-risk B-ALL. The screen, which uses tumor-derived mRNA to assay for transcripts that can substitute for IL3 signaling, is broadly applicable to other tumor types, as many gain-of-function alterations in epithelial and mesenchymal malignancies (e.g., mutant EGFR, KIT, ERBB2, ALK, and EWS) confer IL3 independence in BaF3 cells (29-34). The alterations identified by the screen are functionally relevant and therefore attractive therapeutic targets.. Our data suggests that routine screening of B-ALL for CRLF2 expression, either by IHC or flow cytometry, offers prognostic value. CRLF2 overexpression was associated with high-risk disease in children and a dismal prognosis in adults. Marked enrichment of the adult CRLF2 overexpression signature among pediatric B-ALL suggests that CRLF2 overexpression drives a similar disease in children and adults. Like FLT3 mutations in acute myelogenous ...

MicroRNA-142 (miR-142) is a versatile posttranscriptional regulator that plays a crucial role in the regulation of both innate and adaptive immune responses. Abrogation of miR-142 expression in mice results in a profound immunodeficiency that is characterized by hypoimmunoglobulinemia and failure to mount robust humoral immune responses to soluble antigen challenges. Paradoxically, miR-142−/− mice display a significant expansion of the B cell compartment due to the accumulation of immature and mature B lymphocytes. To better understand the role of miR-142 in B cell ontogenesis, we examined the early B cell development in miR-142−/− mice using the Hardy fraction analysis. We found that miR-142 deletion results in a significant increase in the frequency of the pro-B and large pre-B cells (Fractions B and C), while the pre-pro-B cell population (Fraction A) decreased. In contrast, miR-142 ablation had little effect on the frequency of small pre-B cell and immature B cell populations. ...

Daniel Griffin provides a clinical report on COVID-19, then we discuss decline of virus-specific bone marrow B cells within a year after influenza vaccination, the push to release SARS-CoV-2 vaccines before completion of phase 3 trials, and absence of evidence for infectious virus in aerosols.. ...

PHILADELPHIA--At Long Beach Community Medical Center, the addition, in 1993, of a new radiation therapy facility and a new cancer center spurred the development of clinical pathways (or practice guidelines) for radiation therapy and breast cancer. 1

Early, low-risk International Prognostic Scoring System (IPSS) myelodysplastic syndrome (MDS) is a heterogeneous disorder where the molecular and cellular hematopoietic defects are poorly understood. To gain insight into this condition, we analyzed gene expression profiles of marrow CD34+ progenitor cells from normal-karyotype, low-blast-count MDS patients, age-matched controls, and patients with non-MDS anemia. Given the heterogeneity of early MDS, a surprisingly consistent finding was decreased expression of B-cell lineage-affiliated genes in MDS patients compared with healthy controls and 3 of 5 samples with non-MDS anemia. Both patients with non-MDS anemia with reduced B-cell gene expression were on chemotherapy. In 25 of 27 of the original samples and 9 further MDS samples, Taqman real-time polymerase chain reaction (PCR) confirmed these data. Flow cytometry on unfractionated marrow from independent samples also demonstrated reduced B-cell progenitors in MDS patients compared with healthy controls.

New insights into human B cell biology. B cells are highly important white blood cells known as lymphocytes and are part of the adaptive immune system. B cells have a specialised receptor on their cell surface (B cell receptor, BCR) which recognises specific proteins. Upon activation, B cells produce antibodies which bind antigens like e.g. molecules from pathogens or vaccines. The drawback of a vast range of different B cell receptors is the potential that some of the receptors recognise self-antigens which can then result in auto-immune disorders. The bone marrow continuously releases immature B cells into the blood stream. A high proportion of these so-called transitional B cells are able to recognise self-antigens via their BCR. It has been unknown where in the body these auto-reactive cells are checked and removed from the circulation. A recent publication by Anna Vossenkämper and Jo Spencer (Kings College) tracked the fate of human transitional B cells and identified that these cells ...

Adult immune-defective mice resemble the B cells of normal neonatal mice, but not bone marrow B cells of adult normal mice with regard to their susceptibility to tolerance induction. A different approach to the analysis of the tolerance susceptibility of immune-defective mice was taken by McKearn and Quintans (1980), who preincubated the tolerogen TNP-fowl y-globulin (TNP-FGG) with B cells of immune-defective or normal mice prior to challenge with the TI-1 antigens TNP-BA or TNP-LPS. 94 ? 74 ? 1978b). D. SUSCEPTIBILITY TO TOLERANCE The susceptibility of CBA/N B cells to tolerance induction was of particular importance in view of the functional defects demonstrated in these cells when analyzed with TI-2 antigens or B-cell mitogens. A number of approaches have been employed in studies on this subject (E. , 1978a,b). In early studies it had been demonstrated that a larger proportion of neonatal splenic B cells and a smaller proportion of adult bone marrow B cells were sensitive to tolerance ...

Hematogones have a characteristic profile of CD38++, CD10+, D19+, sIg-, Fc receptor negative, CD20- or dim, and a cluster often found dimmer and smaller on the CD45/log side scatter display. The CD10, CD38, CD45 combination can be useful. The goal is to distinguish ALL from normal precusor B cells. For detection at a low level (,2%) it is useful to know the original antigenic fingerprint of the ALL clone.. Flow cytometric analyses of bone marrow cells demonstrates a spectrum beginning from early B-cell precursors (CD10+,CD19+, TdT+, HLA-Dr+) to mature sIg-bearing B cells in these patients, intermediate forms, and mature lymphocytes. DNA content is normal, and no clonal abnormality is identified by either cytogenetic or immunoglobulin and T-cell receptor (TCR) gene rearrangement studies.. The earliest recognizable B-lineage precursors expresses CD34 in combination with CD38, CD19, high levels of CD10(bright), and low levels of CD22 and lacking CD20. These cells progress to the next stages by ...

TY - JOUR. T1 - Aged mice exhibit distinct B cell precursor phenotypes differing in activation, proliferation and apoptosis. AU - Van der Put, Elaine. AU - Sherwood, Erin M.. AU - Blomberg, Bonnie B. AU - Riley, Richard L. PY - 2003/10/1. Y1 - 2003/10/1. N2 - Senescence in murine models is associated with a reduction, albeit heterogeneous, in bone marrow pre-B cells. We have categorized aged BALB/c mice into two phenotypes based on their patterns of pre-B/pro-B cell loss. Each phenotype is characterized by distinct responses to the growth cytokine IL-7 and capacity for survival in vitro. A moderate loss of late-stage pre-B cells (25-80%) coincided with decline in proliferation to rmIL-7. This was also associated with a decrease in the frequency of pro-B cells which increased phosphotyrosine content upon IL-7 stimulation, an indicator of early activation events. A severe loss of pre-B cells (,80%) resulted in a reduced pro-B cell pool which retained normal activation and proliferative ...

Early B cell development and late B cell maturation are regulated by signals emanating from the pre-B cell receptor (BCR) and BCR, respectively. During maturati...

Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. In the cell membrane of erythrocytes, it is required to maintain phosphatidylserine (PS) in the inner leaflet preventing its exposure on the surface. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized PS is a phagocytic signal for splenic macrophages (PubMed:26944472). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules (By similarity). Required for B cell differentiation past the pro-B cell stage (By similarity). Seems to mediate PS flipping in pro-B cells (By similarity). May be involved in the transport of cholestatic bile acids (By similarity).

Spi-C is an Ets family transcription factor closely related to PU.1 and Spi-B. Expression of Spi-C is developmentally regulated in the B-cell lineage, but its function remains unknown. To determine the function of Spi-C in B-cell development, we generated mice expressing a B-cell-specific Spi-C transgene under the control of the IgH intronic enhancer. Spi-C transgenic mice had 50% fewer B cells than wild-type littermates. Flow cytometric analyses showed that splenic transitional B cells and bone marrow pre-B or immature B cells from transgenic mice were dramatically reduced compared with those of wild type ...

Clone REA780 recognizes the CD20 antigen, a non-glycosylated transmembrane protein of 33-37 kDa that is expressed on B lineage cells from the pre-B cell stage to the B cell lymphoblast stage. The antigen is further expressed on most malignant B cells. CD20 is not found on early B cell progenitors or plasma cells. Oligomers of CD20 form a Ca2+ channel and might function in the regulation of local responses during B cell activation.Additional information: Clone REA780 displays negligible binding to Fc receptors. - Nederland

Involved in a multitude of developmental processes, PAX5 expression is not only continuously required for B cell lineage commitment during early B cell development but also for B lineage maintenance, involved in the regulation of the CD19 gene, a B-lymphoid-specific target gene ...

B cells represent a critical component of the immune system: in the absence of these cells, the ability to fight infections and to establish long-term protectiv...

Start-up company Micromet owned the intellectual property rights, and when it was acquired these were transferred to Amgen, which now markets Blincyto in the United States following the drugs approval by the FDA. Prof. Thomas Sommer, interim Scientific Director at MDC, says: The MDCs basic research has borne fruit. The path to drug approval is often a long and difficult one, but the example set by Blinatumomab and other promising MDC projects show that we are on the right track.. Blincyto is used to treat B-cell acute lymphoblastic leukemia (full name: Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia or pre-B-cell ALL). In the U.S., Blincyto was granted breakthrough therapy designation for treating this specific type of leukemia. Patients suffering from the disease usually have a prognosis of only a few months survival time. The drug signifies new hope for these patients. It will be used in situations where conventional treatment will no longer lead to recovery ...

Children with trisomy 21/Straight down syndrome (DS) are in high risk to build up acute megakaryoblastic leukemia (DS-AMKL) as well as the related transient leukemia (DS-TL). whereas in breasts cancer, high appearance Tmem26 degrees of mediate down-regulation of (HER2) and (HER3), thus suppressing tumor development (Scott et al. 2007). The homolog is certainly involved with translocations found in precursor B-cell acute lymphoblastic leukemia (pre-B ALL) and myelodysplastic syndrome (MDS) (Sonoki et al. 2005; Bousquet et al. 2008). However, RS-127445 the role of Hsa21-encoded in leukemogenesis has not been defined. Physique 1. Hsa21-encoded is usually up-regulated in AMKL patient samples. (and four other miRNAs (in hematopoiesis and leukemogenesis. Using a genetic approach, we exhibited that, in both murine and human contexts, overexpression of led to specific hyperproliferation and enhanced self-renewal capacity of megakaryocytic progenitors (MPs) and megakaryocytic/erythroid progenitors ...

Cancr y pen ar gwddf, sarcoma cell piswydden, canser y fron, neoplasm troffoblastig, canser sefnigol, crydcymalau gwynegol, crydcymalau gwynegol ieuengaidd, osteosarcoma, mycosis ffyngaidd, neoplasm diniwed ar yr ysgyfaint, canser y ceilliau, liwcemia, canser y stumog, lymffoma, acropustulosis, polyarthritis, sbondylitis asiol, precursor t-lymphoblastic lymphoma/leukemia, granulomatosis wegener, liwcemia myeloid aciwt, precursor t-cell acute lymphoblastic leukemia, beichiogrwydd ectopig, polymyositis, diffuse large b-cell lymphoma, t-cell lymphoma, polymyalgia rheumatica, llid briwiol y coluddyn, lymffoma ddi-hodgkin, uveitis, bone sarcoma, lewcemia promyelocytig acíwt, b-cell lymphoma, osteoarthritis susceptibility 1, gwynegon, temporal arteritis, systemic-onset juvenile idiopathic arthritis, central nervous system lymphoma, precursor b-cell acute lymphoblastic leukemia, pemffigaidd pothellog ...

This Podcast features an interview with Bridget Wilson, author of a Research Article that appears in the 29 November 2016 issue of Science Signaling, about pre-B cell receptor (pre-BCR) signaling in B cell precursor acute lymphoblastic leukemia (BCP-ALL). Signaling through the pre-BCR, an immature form of the BCR, promotes the survival of B cell progenitors and has been implicated in the pathology of BCP-ALL. Erasmus et al. found that pre-BCRs formed transient homomeric complexes that correlated with pro-survival signaling. Preventing homotypic interactions between pre-BCRs sensitized B cells to chemotherapeutic agents, suggesting that interfering with such interactions may improve the efficacy of existing chemotherapies for BCP-ALL.. Listen to Podcast ...

We found that BTG2 is up-regulated upon pre-B cell differentiation and that an induced expression of BTG2 in pre-B cells stops their proliferation, explains Dr. Elmar Dolezal, the first author of the published paper. How the BTG2/PRMT1 complex stops pre-B cell proliferation was shown by Dr. David Medgyesi: once activated by BTG2, PRMT1 specifically methylates the protein CDK4, thereby preventing its function in the cell cycle and further cell proliferation.. Interestingly, many tumor cells have either deleted the BTG2 gene or have silenced it. For example it is hardly expressed in B-Cell Acute Lymphoblastic Leukemia (B-ALL), the most common type of cancer in children. Using a mouse model, the authors of the study have shown that reintroducing BTG2 in such B-ALL tumor cells prevents further tumor development.. We have discovered how BTG2 works as a tumor suppressor in pre-B cells and this may help to better understand and possibly develop a better treatment of B-ALL tumors, summarizes Reth. ...

Pre-BCR signaling is normally a vital gate in B cell advancement in which B-lineage cells articulating functional IgH -string are selectively extended. set with typical IgL (1, 6, 7). Research in mouse possess proven that 50% of -stores from early pre-B cells perform not really set with SL, and these cells are most likely removed in the BM environment (8). Developmental pads at the pre-B cell stage are generally credited to an incapacity of -stores to type a signal-competent pre-BCR (6, 9). Situations in which limited -stores enable for regular pre-B cell advancement have got been credited to compensatory systems of Adriamycin IC50 CDR3 that give pre-BCR development (6, 9, 10). We make use of a mutant bunny model program to investigate a developing bottleneck at the pre-B cell stage linked with usage of a particular VH gene. The mutant bunny was uncovered 25 y ago through the research of bunny VH allotypes (11). Serum evaluation of youthful rabbits showed ski slopes cutbacks in the VHa-allotype ...

Up to now long-term in vitro growth of pro-B cells was thought to require stromal cells. However, here we show that fetal liver (FL) and bone marrow (BM) derived pro-B cells can be propagated long-term in stromal cell-free cultures supplemented with IL-7, stem cell factor and FLT3 ligand. Within a week, most cells expressed surface CD19, CD79A, λ5, and VpreB antigens and had rearranged immunoglobulin D-J heavy chain genes. Both FL and BM pro-B cells reconstituted the B-cell compartments of immuno-incompetent Rag2-deficient mice, with FL pro-B cells generating follicular, marginal zone (MZB) and B1a B cells, and BM pro-B cells giving rise mainly to MZB cells. Reconstituted Rag2-deficient mice generated significant levels of IgM and IgG antibodies to a type II T-independent antigen; mice reconstituted with FL pro-B cells generated surprisingly high IgG1 titers. Finally, we show for the first time that mice reconstituted with mixtures of pro-B and pro-T cells propagated in stromal cel... ...

TIM-1 defines a human regulatory B cell (Bregs) population that is altered in frequency and function in systemic sclerosis (SSc) patients. TIM-1 is a unique marker for the identification of a human IL-10+ Breg subpopulation which is partially superimposed with transitional B cells. Alterations in TIM-1+ B cells could contribute to the development of autoimmune diseases such as SSc. PubMed, Arthritis Res Ther, 2017 Jan 19;19(1):8. (Also see B Cells and T Cells) This item was posted in the ISN Newsroom. Please check the newsroom daily for updates on scleroderma and other related articles ...

B Cells, Chromatin, Chromatin Immunoprecipitation, DNA, Genes, Immunoprecipitation, Lymphocyte, Lymphopoiesis, Pre-b Cell, Pre-b Cell Receptor, Pro-b Cells, Tissue, Transcription Factor, Transcriptional Network, Zinc, Biology, Data Collection, Dissection, Engineering, Hands

In August 2019, the U.S. Food and Drug Administration granted breakthrough therapy designation to an experimental immunotherapy being developed in the Center for Cancer Research (CCR) for the treatment of B-cell acute lymphoblastic leukemia (ALL), a type of blood cancer. The designation will advance CCRs development and testing of an immunotherapy for children and young

We originally cloned and identified murine Zizimin2 (Ziz2, Dock11) as a guanine nucleotide exchange factor (GEF) for Cdc42 and demonstrated that it activated the formation of filopodia. Since its expression pattern is restricted in immune tissues and Rho GTPases such as Cdc42 function in B cell deve …

Results High expression levels of TLR7 in SLE patients positively correlated with IFN signature and disease activity, but not with BAFF titers. SLE patients with high levels of TLR7 (TLR7hi group) showed an expansion of CD19+CD38highCD24highCD10+ TR B cells. Overall, frequencies of TR B cells positively correlated with the levels of TLR7, but not TLR9. SLE patients, carrying a risk G allele, had increased TLR7 expression and TR cell frequencies, compared to non-risk allele carriers. TLR7hi SLE patients showed increased autoantibody titers and skewing towards Sm/RNP antigens. Upon IFNα priming, TR B cells up-regulated TLR7 and differentiated into plasmablasts in response to TLR7-ligand stimulation. ...

Leukemogenesis is a multi-step process which involves the disruption of the normal development of a hematopoetic cell. Precursor-B acute lymphoblastic leukemia (Pre-B ALL) is one such example of the process of leukemogenesis that results from deregulated early B cell development in the bone marrow. Typically, checkpoints which are present at every stage of development safeguard an early B cell from leukemic transformation. This thesis focuses on two such critical cell signaling mechanisms that act at the pre-B cell receptor (pre-BCR) checkpoint (Fraction C), and thereby protect the cell from overt leukemogenesis. While one of the mechanisms protects the B cell from acquiring genetic alterations, the other eliminates deleterious B cells by a process known as negative selection. ❧ In the first half of this thesis, we highlight the novel role of IL7R as the guardian of the B cell genome before Fraction D. We show that IL7R carries out this function by preventing pre-mature expression of AID and ...

Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, and B-cell is the most common type of ALL. In childhood ALL, the most important prognostic factor is treatment and without effective treatment, ALL is a fatal illness. So far, different treatment protocols are employed for ALL chemotherapy. Each of these treatment protocols has different side effects and prognosis.In the current study, the children oncology group (COG) protocol was compared with the modified protocols, based on the Berlin-Frankfurt-Munster (BFM) protocol, called the Mofid Childrens Hospital protocol (MCHP). The current study was conducted on 108 patients; 51 patients with COG protocol and 57 with MCHP; 61.1% of patients had pre B-cell ALL type and 38.9% had early pre B-cell ALL type.Induction failures in the COG and MCHP groups were 5.9% and 10.5%, respectively (P = 0.390). In the two groups, the most common recurrence sites were bone marrow (BM) and central nervous system (CNS). Moreover, the incidence of

Sigma-Aldrich offers abstracts and full-text articles by [N Yuan, L Song, W Lin, Y Cao, F Xu, S Liu, A Zhang, Z Wang, X Li, Y Fang, H Zhang, W Zhao, S Hu, J Wang, S Zhang].

Principal Investigator：KARASUYAMA Hajime, Project Period (FY)：1996 - 1997, Research Category：Grant-in-Aid for Scientific Research (B), Section：一般, Research Field：Immunology

Here we describe a protocol for isolating subsets of precursor B-cells from umbilical cord blood. A sufficient quantity and quality of ...

Amanda and Tim Apfel have received an outpouring of community support since their 3-year-old daughter, Piper, was diagnosed with B-cell acute lymphoblastic leukemia. They are used to putting their

Two infants with relapsed, refractory B-cell acute lymphoblastic leukemia went into complete remission after being treated with CD19-targeting CAR T cells derived from an unmatched donor. The study is the first to demonstrate that a universal form of CAR T-cell therapy can be safely utilized. ...

Complete information for BLACE gene (RNA Gene), B-Cell Acute Lymphoblastic Leukemia Expressed, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

A parade recently passed by Charlotte Lalas home after she wrapped up her first year of treatment for B-Cell Acute Lymphoblastic Leukemia.

Remember first that the human body nearly always, although there are exceptions, rejects any non-genetically identical graft placed into it, and therefore one cannot prepare a general colony of B-cells to confer immunity to the population at large. However, in principle, there is no impediment to removing B-cell progenitors in an individual, conditioning them to produce antibodies (which would be an artificial analogue of the natural process of Clonal Selection), and re-injecting these differentiated B-cells into the patient. To my knowledge this process is currently beyond the capacity of our current cell culture techniques, as B-cell differentiation is controlled by an elaborate cell-signaling process, and even if it was feasible, it would remain impractical for several reasons. First, since the B-cell products, antibodies, can be transferred humorally, and should be tolerated by the general population, many existing treatments simply involve injecting antibodies into the patients ...

Sigma-Aldrich offers abstracts and full-text articles by [J Cho, J Seo, C H Lim, L Yang, T Shiratsuchi, M-H Lee, R R Chowdhury, H Kasahara, J-S Kim, S P Oh, Y J Lee, N Terada].

Up to now long-term in vitro growth of pro-B cells was thought to require stromal cells. However, here we show that fetal liver (FL) and bone marrow (BM) derived pro-B cells can be propagated long-term in stromal cell-free ...

Aiolos II is dynamic gas mixer and the last generation of GasMix™ product - It used to save money, gain in flexibility and perform multi-point calibration

This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab, may induce changes in bodys immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether standard combination chemotherapy is more effective than blinatumomab in treating relapsed B-cell acute lymphoblastic leukemia ...

This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Monoclonal antibodies, such as blinatumomab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether standard combination chemotherapy is more effective than blinatumomab in treating relapsed B-cell acute lymphoblastic leukemia ...

TY - JOUR. T1 - Six candidate miRNAs associated with early relapse in pediatric b-cell acute lymphoblastic leukemia. AU - Amankwah, Ernest K.. AU - Devidas, Meenakshi. AU - Teachey, David T.. AU - Rabin, Karen R.. AU - Brown, Patrick A.. PY - 2020/6. Y1 - 2020/6. N2 - Background/Aim: Few studies have evaluated the role of miRNAs in pediatric acute lymphoblastic leukemia (ALL) relapse and a consensus of a clinically significant miRNA signature is yet to be identified. In this study, we evaluated miRNAs associated with pediatric B-ALL early relapse in two independent sample sets. Materials and Methods: We performed global miRNA profiling on diagnostic bone marrow specimens from six early relapse (?3 years after diagnosis) and six age- and cytogenetics-matched prolonged remission (?4 years) patients (first set) and an independent set of 14 early relapse and 14 matched prolonged remission specimens (second set). Results: Twelve and 39 top differentially expressed miRNAs were observed in the first ...

B cell Ag receptor (BCR) signaling changes dramatically during B cell development, resulting in activation in mature B cells and apoptosis, receptor editing, or anergy in immature B cells. BCR signaling in mature B cells was shown to be initiated by the translocation of the BCR into cholesterol- and sphingolipid-enriched membrane microdomains that include the Src family kinase Lyn and exclude the phosphatase CD45. Subsequently the BCR is rapidly internalized into the cell. Here we show that the BCR in the immature B cell line, WEHI-231, does not translocate into lipid rafts following cross-linking nor is the BCR rapidly internalized. The immature BCR initiates signaling from outside lipid rafts as evidenced by the immediate induction of an array of phosphoproteins and subsequent apoptosis. The failure of the BCR in immature B cells to enter lipid rafts may contribute to the dramatic difference in the outcome of signaling in mature and immature B cells.

This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute

BACKGROUND: The early B lymphopoiesis in mammals is regulated through close interactions with stromal cells and components of the intracellular matrix in the bone marrow (BM) microenvironment. Although B lymphopoiesis has been studied for decades, th

Precursor B cell acute lymphoblastic leukemia (BCP-ALL) constitutes the leading cause of cancer-related death in children. While chromosomal alterations contribute to BCP-ALL pathogenesis, they are insufficient for leukemia development. Epidemiological data and evidence from a mouse model suggest that immune responses to infections may trigger the emergence of leukemia, but the mechanisms remain unclear. Here, we show that T helper (Th) cells from bone marrow of pediatric BCP-ALL patients can be attracted and activated by autologous BCP-ALL cells. Bone-marrow Th cells supportively interacted with BCP-ALL cells, inducing upregulation of important surface molecules and BCP-ALL cell proliferation. These Th cells displayed a Th1-like phenotype and produced high levels of IFN-γ. IFN-γ was responsible for the upregulation of CD38 in BCP-ALL cells, a molecule which we found to be associated with early relapse, and accountable for the production of IP-10, a chemokine involved in BCP-ALL migration and ...

Common variable immune deficiency is definitely a heterogeneous immune deficiency characterized by reduced serum immunoglobulins and a lack of antibodies. As these ethnicities are time-consuming, not standardized and the results are based on the activators used, more recently CVID subjects have been classified from the phenotype of unstimulated peripheral blood B cells. Here, we discuss the B-cell problems in CVID and the medical consequences of these abnormalities, and explore how these studies may lead to a better understanding of this complex immune defect. B lymphocytes arise from hemopoietic stem cells in the bone marrow. Early progenitor B cells are characterized by progressive variable-diversity-joining recombination, first of the Ig weighty chain, followed by the surrogate light chains, to produce a pre-B-cell receptor (BCR) [5]. B cells are characterized by the surface expression of CD19, among other characteristics. Progression to the immature B cell occurs after a mature light chain ...

Despite the fact that many therapeutic strategies have been adopted to delay the development of sepsis, sepsis remains one of the leading causes of death in noncoronary intensive care units. Recently, sepsis-3 was defined as life-threatening organ dysfunction due to a dysregulated host response to infection. Here, we report that swiprosin-1 (also known as EFhd2) plays an important role in the macrophage immune response to LPS-induced or cecal ligation and puncture-induced (CLP-induced) sepsis in mice. Swiprosin-1 depletion causes higher mortality, more severe organ dysfunction, restrained macrophage recruitment in the lung and kidney, and attenuated inflammatory cytokine production (including IL-1β, IL-6, TNF-α, IL-10, and IFN-γ). The immunosuppression caused by swiprosin-1 deficiency is manifested by impaired bactericidal capacity and decreased HLA-DR expression in macrophages. Swiprosin-1 affects the activation of the JAK2/STAT1/STAT3 pathway by regulating the expression of IFN-γ receptors ...

B and T lymphocytes are generated from hematopoietic stem cells during both fetal and adult life. A critical unresolved issue is whether the differentiation pathways in lymphopoiesis are the same in fetal and adult animals or whether they differ, similar to the hemoglobin switch in erythropoiesis. We report here that a developmental switch occurs in B lymphopoiesis. We isolated pro-B cells (i.e., cells that have initiated, but not completed, heavy-chain gene rearrangement) from fetal and adult sources and investigated their B-cell progeny generated both in vitro and in vivo. Most of the cells from fetal liver, but few from adult bone marrow, expressed CD5. Further, fetal pro-B cells failed to generate cells expressing high levels of IgD in severe combined immunodeficiency mice, whereas adult pro-B cells gave rise to CD5-B cells bearing IgD at levels comparable to the bulk of cells in the spleen of adult mice. Thus, all committed B progenitors in fetal liver of day 16 gestation mice give rise to