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The occurrence and development of tumors are closely associated with abnormalities in the immune system's structure and function, with tumor immunotherapy being intricately linked to the tumor microenvironment (TME). Early studies on lymphocytes within the TME primarily concentrated on T cells. However, as research has advanced, the multifaceted roles of tumor-infiltrating B cells (TIL-Bs) in tumor immunity, encompassing both anti-tumor and pro-tumor effects, have garnered increasing attention. This paper explored the composition of the TME and the biological characteristics of TIL-Bs, investigating the dual roles within the TME to offer new insights and strategies for tumor immunotherapy. [Display omitted] • Dual roles of tumor-infiltrating B cells in tumor microenvironment: anti-tumor and pro-tumor effects. • Tumor-infiltrating B cells boost anti-tumor immunity via antigen presentation, antibody production, cytokine secretion, etc. • Regulatory B cells aid tumor immune evasion by releasing suppressive cytokines, specific antibodies, and metabolites. • Insights into Tumor-infiltrating B cells may offer potential new targets for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antigen-presenting cells facilitating antibody production but also as sensors, coordinators, and regulators of the immune response. In particular, B cells can regulate the T cell activation process through their participation in antigen presentation, production of proinflammatory cytokines (bystander activation or suppression), and contribution to ectopic lymphoid aggregates. Such an important interplay between B and T cells makes therapeutic depletion of B cells an attractive treatment strategy. The last decade, anti-B cell therapies using monoclonal antibodies against B cell surface molecules have evolved into a rational approach for successfully treating autoimmune neurological disorders, even when T cells seem to be the main effector cells. The paper summarizes basic aspects of B cell biology, discusses the roles of B cells in neurological autoimmunities, and highlights how the currently available or under development anti-B cell therapeutics exert their action in the wide spectrum and immunologically diverse neurological disorders. The efficacy of the various anti-B cell therapies and practical issues on induction and maintenance therapy is specifically detailed for the treatment of patients with multiple sclerosis, neuromyelitis-spectrum disorders, autoimmune encephalitis and hyperexcitability CNS disorders, autoimmune neuropathies, myasthenia gravis, and inflammatory myopathies. The success of anti-B cell therapies in inducing long-term remission in IgG4 neuroautoimmunities is also highlighted pointing out potential biomarkers for follow-up infusions. [ABSTRACT FROM AUTHOR]

The immune system employs complex tolerance mechanisms in order to avoid harmful autoimmunity, yet autoantibodies are frequently observed in cancer. In a paper in Cell , Mazor et al. report that autoantibodies produced by tumor-infiltrating B cells in human ovarian cancer frequently recognize the self-protein matrix metalloproteinase 14 (MMP14) through two distinct mechanisms of tolerance disruption. [ABSTRACT FROM AUTHOR]

• SHC014748M was proved to be more selective for PI3Kδ inhibition relative to other class i PI3K enzymes. • SHC014748M showed in vitro activity in most of 23 B lymphoma cell lines and primary CLL cells and also inhibited phosphorylation of AKT, targets downstream of PI3Kδ. • In vivo study revealed that SHC014748M significantly reduced lymphoma cell growth in the treatment group compared with control mice. • SHC014748M seemed to be a novel promising compound in the treatment of B cell lymphomas and CLL. PI3Kδ (phosphatidylinositol 3-kinase-δ), one of the class I PI3Ks, is found expressed primarily in leukocytes and plays an essential role in B-cell development and function. This provides a rationale for the development of small molecule inhibitors that selectively target p110δ for patients with indolent non-Hodgkin lymphomas. Here in this paper, we comprehensively evaluated the in vitro and in vivo antitumor activity of SHC014748M, an oral selective inhibitor of PI3Kδ under Phase I clinical evaluation. Biochemical and cell-based assays were used to measure compound potency and selectivity in lymphoma cell lines as well as primary chronic lymphocytic leukemia (CLL) cells. Scid mice were subcutaneously inoculated with the SU-DHL-6 cell line. SHC014748M was more selective for PI3Kδ inhibition relative to other class I PI3K enzymes and showed in vitro activity in most of 23 B lymphoma cell lines and primary CLL cells. SHC014748M also inhibited phosphorylation of AKT, targets downstream of PI3Kδ, in both lymphoma cells and primary CLL cells. In vivo study revealed that SHC014748M significantly reduced lymphoma cell growth in the treatment group compared with control mice. CCL4, CCL17, CCL22 and CXCL13 in patient serum decreased sharply after SHC014748M treatment. According to the results, SHC014748M appeared to be a novel promising compound in the treatment of B cell lymphomas and CLL. [ABSTRACT FROM AUTHOR]

Thiopurine drugs are immunomodulatory antimetabolites relevant for pediatric patients characterized by dose-dependent adverse effects such as myelosuppression and hepatotoxicity, often related to inter-individual differences, involving the activity of important enzymes at the basis of their biotransformation, such as thiopurine S-methyltransferase (TPMT). Surface Enhanced Raman Scattering (SERS) spectroscopy is emerging as a bioanalytical tool and represents a valid alternative in terms of affordable costs, shorter analysis time and easier sample preparation in comparison to the most employed methods for pharmacokinetic analysis of drugs. The aim of this study is to investigate mercaptopurine and thioguanine pharmacokinetics by SERS in cell lysates of a B-lymphoblastoid cell line (NALM-6), that did (TPMT*1) or did not (MOCK) overexpress the wild-type form of TPMT as an in vitro cellular lymphocyte model to discriminate between cells with different levels of TPMT activity on the base of the amount of thioguanosine nucleotides (TGN) metabolites formed. SERS analysis of the cell lysates was carried out using SERS substrates constituted by Ag nanoparticles deposited on paper and parallel samples were used for quantification of thiopurine nucleotides with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A direct SERS detection method has been set up that could be a tool to study thiopurine drug pharmacokinetics in in vitro cellular models to qualitatively discriminate between cells that do and do not overexpress the TPMT enzyme, as an alternative to other more laborious techniques. Results underlined decreased levels of TGN and increased levels of methylated metabolites when TPMT was overexpressed, both after mercaptopurine and thioguanine treatments. A strong positive correlation (Spearman's rank correlation coefficient rho = 0.96) exists between absolute quantification of TGMP (pmol/1 x 106 cells), obtained by LC-MS/MS, and SERS signal (intensity of TGN at 915 cm−1). In future studies, we aim to apply this method to investigate TPMT activity in pediatric patients' leukocytes. • A direct SERS method to qualitatively discriminate between cells that do and do not overexpress TPMT is discussed. • LC-MS/MS and SERS parallel analysis of cell lysate detect decreased levels of TGN when TPMT is overexpressed. • Quantification by LC-MS/MS of 12 thiopurine metabolites in human B-lymphoblastoid cell line is reported. [ABSTRACT FROM AUTHOR]

Due to the rapid development of DNA microarray technology, a large number of microarray data come into being and classifying these data has been verified useful for cancer diagnosis, treatment and prevention. However, microarray data classification is still a challenging task since there are often a huge number of genes but a small number of samples in gene expression data. As a result, a computational method for reducing the dimension of microarray data is necessary. In this paper, we introduce a computational gene selection model for microarray data classification via adaptive hypergraph embedded dictionary learning (AHEDL). Specifically, a dictionary is learned from the feature space of original high dimensional microarray data, and this learned dictionary is used to represent original genes with a reconstruction coefficient matrix. Then we use a l 2, 1 -norm regularization to impose the row sparsity on the coefficient matrix for selecting discriminate genes. Meanwhile, in order to capture the localmanifold geometrical structure of original microarray data in a high-order manner, a hypergraph is adaptively learned and embedded into the model. An iterative updating algorithm is designed for solving the optimization problem. In order to validate the efficacy of the proposed model, we have conducted experiments on six publicly available microarray data sets and the results demonstrate that AHEDL outperforms other state-of-the-art methods in terms of microarray data classification. Unlabelled Table AHEDL Adaptive Hypergraph Embedded Dictionary Learning ADMM Alternating Direction method of Multipliers SVM Support Vector Machine RF Random Forest k-NN k-Nearest Neighbor CV cross validation MSVM-RF Multiclass Support Vector Machine-Recursive Feature Elimination KernelPLS Kernel Partial Least Squares WLMGS Weight Local Modularity based Gene Selection GRSL-GS Gene Selection via Subspace Learning and Manifold Regularization LNNFW Local-Nearest-Neighbors-based Feature Weighting for Gene Selection RLR Regularized Logistic Regression ACC accuracy SD standard deviations ANOVA Analysis of Variance DF Degrees of Freedom SS Sum-of-Square MS Mean Sum-of-Square F F-value Sig statistical significance SRBCT Small Round Blue Cell Tumors GCM Global Cancer Map CLL_SUB_111 B-cell chronic lymphocytic leukemia • We introduce a new gene selection model for microarray data classification. • A dictionary is learned to reconstruct original genes. • A hypergraph is adaptively learned and embedded into the model. • The hypergraph is used to capture the high-order locality of microarray data. • Experiments on six data sets validate the efficacy of the proposed model. [ABSTRACT FROM AUTHOR]

Diagnosing acute leukemia is the necessary prerequisite to treating it. Multi-classification on the gene expression data of acute leukemia is help for diagnosing it which contains B-cell acute lymphoblastic leukemia (BALL), T-cell acute lymphoblastic leukemia (TALL) and acute myeloid leukemia (AML). However, selecting cancer-causing genes is a challenging problem in performing multi-classification. In this paper, weighted gene co-expression networks are employed to divide the genes into groups. Based on the dividing groups, a new regularized multinomial regression with overlapping group lasso penalty (MROGL) has been presented to simultaneously perform multi-classification and select gene groups. By implementing this method on three-class acute leukemia data, the grouped genes which work synergistically are identified, and the overlapped genes shared by different groups are also highlighted. Moreover, MROGL outperforms other five methods on multi-classification accuracy. [ABSTRACT FROM AUTHOR]

This article presents the research papers presented in the Thirteenth Annual ADF Meeting, which was held in November 1985 at Vienna, Austria. The paper on "Tac Antigen Expression by Malignant Lymphocytes Infiltrating the Skin-Pathogenetic Considerations," by V. Groh, U. Kö ller and G. Stingi focuses on T cell proliferation. Some other topics covered are cutaneous lesions in histiocytosis X, HTLV-1 positive primary cutaneous B-cell Lymphoma, and human epidermal, Langerhans cells in culture.

This article presents abstracts for various research papers to be presented in the European Society for Dermatological Research's symposium on September 26-28, 1997. These research papers pertain to subjects like the eortic classification for primary cutaneous lymphomas, different prognosis between cutaneous and systemic lymphoproliferative disorders, parapsoriasis and early cutaneous T cell lymphoma, immunoglobulin gene rearrangement of pseudo B-cell lymphomas and prognostic significance of polymerase chain reaction detectable dominant T lymphocyte clones.

This study reviewed the prognostic effect of tumor-infiltrating B lymphocytes (TIBLs) on solid malignancies, to determine the potential role of TIBLs in predicting cancer patient's prognosis and their response to immunotherapy. A total of 45 original papers involving 11,099 individual patients were included in this meta-analysis covering 7 kinds of cancer. The pooled results suggested that high levels of TIBLs were correlated with favorable OS in lung, esophageal, gastric, colorectal, liver, and breast cancer; improved RFS in lung cancer; and improved DFS in gastrointestinal neoplasms. Additionally, TIBLs were significantly correlated with negative lymphatic invasion in gastric cancer, small tumor size in hepatocellular carcinoma, and negative distant metastasis in colorectal cancer. Additionally, TIBLs were reported as a discriminative feature of patients treated with immunotherapy with improved survival. We concluded that TIBLs play a favorable prognostic role among the common solid malignancie, providing theoretical evidence for further prognosis prediction for solid tumors. • Analyze and review the prognostic value of B cells in solid tumors from different systems. • Assess the relationship between tumor-infiltrating B cells and other clinicopathological parameters. • Evaluate the potential role of B cells in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. In this study, a B cell-deficient mouse model was created by injecting an anti-CD20 antibody. The frequency of tolerogenic dendritic cell (TolDC) was assessed by flow cytometry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The expression of thrombospondin-1 (TSP1) was assessed by quantitative real-time RT-PCR, Western blotting, and methylationspecific PCR. The results showed that B cells were required in the generation of the TGF-β-producing TolDCs in mice. B cell-derived TSP1 converted the latent TGF-β to the active TGF-β in DCs, which generated TGF-β-producing TolDCs. Exposure to IL-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. In conclusion, B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy. [ABSTRACT FROM AUTHOR]

Antibodies are high value therapeutic, diagnostic, biotechnological, and research tools. Combinatorial approaches to antibody discovery have facilitated access to unique antibodies by surpassing the diversity limitations of the natural repertoire, exploitation of immune repertoires from multiple species, and tailoring selections to isolate antibodies with desirable biophysical attributes. The V-gene repertoire of the chicken does not utilize highly diverse sequence and structures, which is in stark contrast to the mechanism employed by humans, mice, and primates. Recent exploitation of the avian immune system has generated high quality, high affinity antibodies to a wide range of antigens for a number of therapeutic, diagnostic and biotechnological applications. Furthermore, extensive examination of the amino acid characteristics of the chicken repertoire has provided significant insight into mechanisms employed by the avian immune system. A paucity of avian antibody crystal structures has limited our understanding of the structural consequences of these uniquely chicken features. This paper presents the crystal structure of two chicken single chain fragment variable (scFv) antibodies generated from large libraries by phage display against important human antigen targets, which capture two unique CDRL1 canonical classes in the presence and absence of a non-canonical disulfide constrained CDRH3. These structures cast light on the unique structural features of chicken antibodies and contribute further to our collective understanding of the unique mechanisms of diversity and biochemical attributes that render the chicken repertoire of particular value for antibody generation. [ABSTRACT FROM AUTHOR]

Abstract: Fetal cattle B-cell development proceeds via a pre-B cell stage that is characterized by the expression of surrogate light chain and recombination activation genes. In this paper, we identify a new member of bovine pre-B lymphocyte genes, VPREB2. Using RT-qPCR, we assess the expression of VPREB2 and three other surrogate light chain genes as well as RAG1 and RAG2 in fetal and adult cattle tissues. The absence of VPREB1, IGLL1, RAG1 and RAG2 expression in adult tissues and the lack of B-lymphoid differentiation in adult bone marrow – OP9 stromal cell co-culture, suggest a decline of B lymphopoiesis in adult cattle. The marked differences in the expression profiles of VPREB2 and VPREB3 in comparison to those of VPREB1, IGLL1 and RAGs suggest that the biological roles of VPREB2 and VPREB3 are unrelated to the pre-B cells. [Copyright &y& Elsevier]

Abstract: In this paper, we investigate the dynamical behavior of in-host viral models with humoral immunity and intracellular delays. For both models, using the method of Lyapunov functional, we establish that the global dynamics are determined by two threshold parameters R 0 and R 1. If R 0 ⩽1, the uninfected equilibrium E 0 is globally asymptotically stable, and the viruses are cleared. If R 1 ⩽1< R 0, the infected equilibrium without B cells response is globally asymptotically stable, and the infection becomes chronic but with no persistent B cells response. If R 1 >1, the infected equilibrium with B cells response is globally asymptotically stable, and the infection is chronic with persistent B cells response. Alone with some numerical simulations. [Copyright &y& Elsevier]

Abstract: Electroporation is a powerful and convenient means for transfection of nonviral vectors into mammalian cells, providing an essential tool for numerous applications including gene targeting via homologous recombination. Recent evidence clearly suggests that high-efficiency gene transfer can be achieved in most cell lines by nucleofection, an electroporation-based transfection method that allows transfected vectors to directly enter the nucleus. In this paper, we analyze the effectiveness of nucleofection for gene targeting using human pre-B cells. For this, we tested 93 different transfection conditions, and found several conditions that gave high (~80%) transfection efficiency with low cytotoxicity (~70% survival rate). Remarkably, under the optimal nucleofection conditions, the gene-targeting efficiency was ~2–5-fold higher than that achieved with conventional electroporation methods. We also found that nucleofection conditions with high transfection efficiency and low cytotoxicity tend to provide high gene-targeting efficiency. Our results provide significant implications for gene targeting, and suggest that nucleofection-based nonviral gene transfer is useful for systematic generation of human gene-knockout cell lines. [Copyright &y& Elsevier]

In the current artificial immune algorithms, the process of activation calculation considers the affinity only, but fails to take into account the relationship between sample features. In response to this deficiency, this paper proposes a new Relation B-cell and Relation B-cell Network Model (RBNM), which is basing on the immune mechanism of clone, mutation and network inhibition. In the method, this relation B-cells were calculated by the relationship between sample features. As a result, in the training and diagnosis process, combining with the relation B-cells, the algorithm can effectively improve the ability of cell association monitoring and finally generate efficient detectors. According to the following performance tests, RBNM classification result is not sensitive to its five parameters and results of the method are competitive among comparison methods. Finally, the algorithm was also applied to the reciprocating compressor faults dataset, and the result reached 99.7%. [Display omitted] • The proposed method can extract the correlation between features. • RBNM has stable performance and strong robustness within the given parameter range. • The method has good performance in the reciprocating compressor dataset. [ABSTRACT FROM AUTHOR]

G2A is a G protein-coupled receptor that is predominantly expressed in lymphoid tissues and macrophages. G2A can be induced by diverse stimuli to cause cell cycle arrest in the G2/M phase in pro-B and T cells. G2A is also expressed in macrophages within atherosclerotic lesions, suggesting G2A involvement in atherosclerosis. Recently, G2A was discovered to possess proton-sensing ability. In this paper, we report another function of G2A, that is, as a receptor for 9-hydroxyoctadecadienoic acid (9-HODE) and other oxidized free fatty acids. G2A, expressed in CHO-K1 or HEK293 cells, showed 9-HODE-induced intracellular calcium mobilization, inositol phosphate accumulation, inhibition of cAMP accumulation, [35S]guanosine 5′-3-O-(thio)triphosphate binding, and MAP kinase activation. Furthermore, G2A was activated by various oxidized derivatives of linoleic and arachidonic acids, but it was weakly activated by cholesteryl-9-HODE. Oxidized phosphatidylcholine (1-palmitoyl-2-linoleoyl) when hydrolyzed with phospholipase A2 also evoked intracellular calcium mobilization in G2A-expressing cells. These results indicate that G2A is activated by oxidized free fatty acids produced by oxidation and subsequent hydrolysis of phosphatidylcholine or cholesteryl linoleate. Thus, G2A might have a biological role in diverse pathological conditions including atherosclerosis. [ABSTRACT FROM AUTHOR]

The sIgG+ lymphoblastoid B cell line CESS spontaneously produces a high amount of nerve growth factor (NGF) and expresses both high affinity (p140Trk-A) and low affinity (p75NTR) NGF receptors. Autocrine production of NGF maintains the survival of CESS cells through the continuous deactivation of p38 MAPK, an enzyme able to induce Bcl-2 phosphorylation and subsequent cytochrome c release and caspase activation. In this paper, we show that NGF induces transcriptional activation and synthesis of MAPK phosphatase 1 (MKP1), a dual specificity phosphatase that dephosphorylates p38 MAPK, thus preventing Bcl-2 phosphorylation. Furthermore, NGF increases MKP-1 protein stability by preventing its degradation through the proteasome pathway. Following NGF stimulation, MKP- protein mainly localizes on mitochondria, suggesting an interaction with p38 MAPK in this compartment. Incubation of CESS cells with MKP-1-specific antisense oligonucleotides induces cell death, which was not prevented by exogenous NGF. By contrast, overexpression of native MKP-1, but not of its catalytically impaired form, inhibits apoptosis induced by NGF neutralization in CESS cells. Thus, the molecular mechanisms underlying the survival function of NGF in CESS B cell line predominantly consist in maintaining elevated levels of MKP-1 protein, which controls p38 MAPK activation. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a late-stage B cell malignancy that has received much attention recently because of its therapeutic susceptibility to proteasome inhibitors. Two papers in this issue of Cancer Cell show that primary MM samples and MM cell lines frequently have mutations in genes encoding regulators and effectors of NF-κB signaling, and that these mutations lead to chronic NF-κB target gene expression, which is required for the viability of these MM tumor cells. These results reveal the molecular basis for constitutive NF-κB activity in many MMs and further validate the NF-κB signaling pathway as an appropriate target for MM therapy. [Copyright &y& Elsevier]

Comments on a paper which examined gene expression profiles of primary cutaneous B-cell lymphomas (CBCL). Value of expression profiling; Classification scheme proposed for CBCL; Use of the hierarchical clustering method to explore the relationship among lymphoma, normal skin and tonsil samples.

Indicator traits used to select pigs for increased resistance to infection or improved health must be heritable and, preferably, be associated with improved performance. We estimated the heritability of a range of immune traits and their genetic and phenotypic correlations with growth performance. We measured immune traits on 589 pigs and performance on 1941 pigs from six farms, three of which were classified as ?high health status? (i.e. specific pathogen-free) and three were of lower health status. All pigs were apparently healthy. Immune traits were total white blood cells (WBC), and peripheral blood mononuclear leucocyte (PBML) subsets positive for CD4, CD8?, gamma delta (??) T cell receptor, CD11R1 (natural killer cell marker), B cell and monocyte markers at the start and the end of standard growth performance tests. At both time points, all immune traits were moderately to highly heritable except for CD8?燩. At end of test, heritability estimates (h2) (?s.e.) were 0.18 (?0.11) for total WBC count. For PBML subset proportions, the heritabilities were 0.52 (?0.14) for ?? TCR燩, 0.62 (?0.14) for CD4燩, 0.44 (?0.14) for CD11R1燩, 0.58 (?0.14) for B cells and 0.59 (?0.14) for monocytes. Farm health status affected the heritabilities for WBC, being substantially higher on lower health status farms, but did not have consistent effects on heritabilities for the PBML subsets. There were significant negative genetic correlations between numbers and proportions of various PBML subsets and performance, at both start and end of test. In particular, the proportion of PBML cells that were CD11R1燩, at end of test, was strongly correlated with daily gain (rg= ?0.72; P< 0.01). There were also weaker but significant negative phenotypic correlations between PBML subsets measured at end of test and performance, for ?? cells, CD8?, CD11R1燩, B cells or monocytes. Phenotypic correlations with daily gain were generally lower at the start of test than at the end of test. These results show that most of the major pig PBML subsets are heritable, and that systemic levels of several of these PBML subsets are genetically negatively correlated with performance. This approach provides a basis for using immune trait markers when selecting boars that can produce higher-performing progeny. [ABSTRACT FROM AUTHOR]