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Kidney International Feb 2008Lupus nephritis (LN) in systemic lupus erythematosus (SLE) remains a major cause of morbidity and end-stage renal disease. While therapies such as corticosteroids,... (Review)
Review
Lupus nephritis (LN) in systemic lupus erythematosus (SLE) remains a major cause of morbidity and end-stage renal disease. While therapies such as corticosteroids, cyclophosphamide, and mycophenolate mofetil have improved outcomes, a significant proportion of patients have refractory disease or are unable to tolerate these agents. Limitations in existing therapies, along with advances in our understanding of the immunopathogenesis of SLE, have resulted in the development of new immunosuppressive and immunomodulatory treatments for SLE/LN. Dysfunction of the B lymphocyte-an important component of adaptive immunity-is thought to be important in the pathogenesis of SLE/LN. The goal of this study is to review our current understanding of the role of B cells in the pathogenesis of SLE, and to discuss new and emerging therapies that selectively target B cells in patients with SLE/LN. Novel strategies discussed include B-cell depletion by the monoclonal antibodies to B-cell markers, rituximab and epratuzumab; 'pharmapheresis' of pathogenic antibodies to dsDNA, by abetimus; blockade of T-cell costimulation of B cells by abatacept, belatacept, BG9588, and IDEC-131; and blockade of B-cell stimulation by belimumab. Preliminary results are promising, but in the absence of large controlled trials, caution must be exercised prior to the widespread use and acceptance of these treatments.
Topics: Antibodies, Monoclonal; B-Lymphocytes; Humans; Lupus Nephritis
PubMed: 18004299
DOI: 10.1038/sj.ki.5002663 -
Clinical and Experimental Immunology Jul 1994In this paper we review different aspects of B cell development on the path from the proB cell to the memory B cell and the plasmocyte. Emphasis is given to the positive... (Review)
Review
In this paper we review different aspects of B cell development on the path from the proB cell to the memory B cell and the plasmocyte. Emphasis is given to the positive and negative selection effects mediated by the changing forms of the surface immunoglobulin (Ig) receptor under successive microenvironments. Positive selection is linked to lambda chain expression at the pro- and preB cell stage in fetal liver and bone marrow. Negative selection takes place when surface (s)IgM is being cross-linked by autoantigens before the immature B cell can leave, or after it has left, the bone marrow. After somatic mutation, major expansion becomes possible for B cells with high-affinity sIg receptors. This takes place in the germinal centres of the secondary lymphoid organs in the context of major histocompatibility complex (MHC) restriction and provided the necessary T cell help is given. Kinetic data on B cell replenishment in the rodent models are used to draw a schematic view of an established B cell repertoire.
Topics: Animals; B-Lymphocytes; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Cell Movement; Cellular Senescence; Fetus; Immunoglobulins; Immunologic Memory; Liver; Mice; Models, Biological; Plasma Cells
PubMed: 8033431
DOI: No ID Found -
Frontiers in Immunology 2022Systemic sclerosis (SSc) is a rare fibrotic rheumatic disease, associated with psychological distress and increased morbidity and mortality due to skin involvement and... (Review)
Review
Systemic sclerosis (SSc) is a rare fibrotic rheumatic disease, associated with psychological distress and increased morbidity and mortality due to skin involvement and internal organ damage. The current understanding of the complex pathogenesis is yet incomplete and disease therapeutic algorithms are far from optimal. Immunologic aberrations are considered key factors for the disease, along with vascular involvement and excess fibrosis. Adaptive immunity and its specialized responses are an attractive research target and both T and B cells have been extensively studied in recent years. In the present review, the focus is placed on B cells in SSc. B cell homeostasis is deranged and B cell subsets exhibit an activated phenotype and abnormal receptor signaling. Autoantibodies are a hallmark of the disease and the current perception of their diagnostic and pathogenetic role is analyzed. In addition, B cell cytokine release and its effect on immunity and fibrosis are examined, together with B cell tissue infiltration of the skin and lung. These data support the concept of targeting B cells as part of the therapeutic plan for SSc through well designed clinical trials.
Topics: Autoantibodies; B-Lymphocyte Subsets; B-Lymphocytes; Fibrosis; Humans; Scleroderma, Systemic
PubMed: 35812378
DOI: 10.3389/fimmu.2022.925741 -
Clinics in Laboratory Medicine Mar 2019B cells shape the alloimmune response through polarized subsets. These cells inhibit or promote immune responses by expressing suppressive or proinflammatory cytokines.... (Review)
Review
B cells shape the alloimmune response through polarized subsets. These cells inhibit or promote immune responses by expressing suppressive or proinflammatory cytokines. Their summed activity dictates the influence of B cells on the alloimmune response. We review the evidence for regulatory B cells and effector B cells in mice and humans, discuss current limitations in their phenotypic identification, and discuss regulatory B cells as a signature for clinical renal allograft tolerance and predictive markers for allograft outcomes. We discuss the effects of therapeutic agents on regulatory B cells and potential approaches to augment their numbers as a therapeutic tool.
Topics: Animals; B-Lymphocyte Subsets; B-Lymphocytes, Regulatory; Biomarkers; Humans; Mice; Transplantation Tolerance; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 30709503
DOI: 10.1016/j.cll.2018.10.011 -
Biochemical Society Transactions Jun 2020The development of B lymphocytes into antibody-secreting plasma cells is central to the adaptive immune system in that it confers protective and specific antibody... (Review)
Review
The development of B lymphocytes into antibody-secreting plasma cells is central to the adaptive immune system in that it confers protective and specific antibody response against invading pathogen. This developmental process involves extensive morphological and functional alterations that begin early after antigenic stimulation. These include chromatin restructuring that is critical in regulating gene expression, DNA rearrangement and other cellular processes. Here we outline the recent understanding of the three-dimensional architecture of the genome, specifically focused on its contribution to the process of B cell activation and terminal differentiation into antibody-secreting cells.
Topics: Adaptive Immunity; Animals; Antibodies; Antibody Formation; Antibody-Producing Cells; B-Lymphocytes; Cell Differentiation; Cell Division; DNA; Gene Expression Regulation; Genome; Humans; Lymphocyte Activation; Plasma Cells; Recombination, Genetic; Transcription, Genetic
PubMed: 32453419
DOI: 10.1042/BST20191104 -
Journal of Immunology Research 2020Antibody-secreting cells (ASCs) play a fundamental role in humoral immunity. The aberrant function of ASCs is related to a number of disease states, including autoimmune... (Review)
Review
Antibody-secreting cells (ASCs) play a fundamental role in humoral immunity. The aberrant function of ASCs is related to a number of disease states, including autoimmune diseases and cancer. Recent insights into activated B cell subsets, including naïve B cell to ASC stages and their resultant cellular disturbances, suggest that aberrant ASC differentiation occurs during autoimmune diseases and is closely related to disease severity. However, the mechanisms underlying highly active ASC differentiation and the B cell subsets in autoimmune patients remain undefined. Here, we first review the processes of ASC generation. From the perspective of novel therapeutic target discovery, prediction of disease progression, and current clinical challenges, we further summarize the aberrant activity of B cell subsets including specialized memory CD11cT-bet B cells that participate in the maintenance of autoreactive ASC populations. An improved understanding of subgroups may also enhance the knowledge of antigen-specific B cell differentiation. We further discuss the influence of current B cell therapies on B cell subsets, specifically focusing on systemic lupus erythematosus, rheumatoid arthritis, and myasthenia gravis.
Topics: Animals; Autoimmune Diseases; B-Lymphocyte Subsets; B-Lymphocytes; Cell Differentiation; Humans; Immunity, Humoral; Immunologic Memory; Immunotherapy; Lymphocyte Activation
PubMed: 32280720
DOI: 10.1155/2020/9518137 -
International Journal of Molecular... Dec 2021Membranous nephropathy (MN) is an important cause of nephrotic syndrome and chronic kidney disease (CKD) in adults. The pathogenic significance of B cells in MN is... (Review)
Review
Membranous nephropathy (MN) is an important cause of nephrotic syndrome and chronic kidney disease (CKD) in adults. The pathogenic significance of B cells in MN is increasingly recognized, especially following the discovery of various autoantibodies that target specific podocytic antigens and the promising treatment responses seen with B cell depleting therapies. The presence of autoreactive B cells and autoantibodies that bind to antigens on podocyte surfaces are characteristic features of MN, and are the result of breaches in central and peripheral tolerance of B lymphocytes. These perturbations in B cell tolerance include altered B lymphocyte subsets, dysregulation of genes that govern immunoglobulin production, aberrant somatic hypermutation and co-stimulatory signalling, abnormal expression of B cell-related cytokines, and increased B cell infiltrates and organized tertiary lymphoid structures within the kidneys. An understanding of the role of B cell tolerance and homeostasis may have important implications for patient management in MN, as conventional immunosuppressive treatments and novel B cell-targeted therapies show distinct effects on proliferation, differentiation and reconstitution in different B cell subsets. Circulating B lymphocytes and related cytokines may serve as potential biomarkers for treatment selection, monitoring of therapeutic response and prediction of disease relapse. These recent advances in the understanding of B cell tolerance in MN have provided greater insight into its immunopathogenesis and potential novel strategies for disease monitoring and treatment.
Topics: Animals; B-Lymphocytes; Cytokines; Disease Management; Glomerulonephritis, Membranous; Humans; Immune Tolerance; Immunosuppressive Agents; Molecular Targeted Therapy
PubMed: 34948358
DOI: 10.3390/ijms222413560 -
Trends in Cancer Dec 2016
Review
Topics: Animals; B-Lymphocyte Subsets; B-Lymphocytes; Cytokines; Disease Progression; Humans; Models, Immunological; Neoplasms; T-Lymphocytes
PubMed: 28626801
DOI: 10.1016/j.trecan.2016.10.010 -
Experimental & Molecular Medicine Jan 2015Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting >90% of the adult population. EBV targets B-lymphocytes and achieves latent infection in a circular... (Review)
Review
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting >90% of the adult population. EBV targets B-lymphocytes and achieves latent infection in a circular episomal form. Different latency patterns are recognized based on latent gene expression pattern. Latent membrane protein-1 (LMP-1) mimics CD40 and, when self-aggregated, provides a proliferation signal via activating the nuclear factor-kappa B, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinase pathways to promote cellular proliferation. LMP-1 also induces BCL-2 to escape from apoptosis and gives a signal for cell cycle progression by enhancing cyclin-dependent kinase 2 and phosphorylation of retinoblastoma (Rb) protein and by inhibiting p16 and p27. LMP-2A blocks the surface immunoglobulin-mediated lytic cycle reactivation. It also activates the Ras/PI3K/Akt pathway and induces Bcl-xL expression to promote B-cell survival. Recent studies have shown that ebv-microRNAs can provide extra signals for cellular proliferation, cell cycle progression and anti-apoptosis. EBV is well known for association with various types of B-lymphocyte, T-lymphocyte, epithelial cell and mesenchymal cell neoplasms. B-cell lymphoproliferative disorders encompass a broad spectrum of diseases, from benign to malignant. Here we review our current understanding of EBV-induced lymphomagenesis and focus on biology, diagnosis and management of EBV-associated B-cell lymphoproliferative disorders.
Topics: B-Lymphocytes; Diagnosis, Differential; Disease Management; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoproliferative Disorders
PubMed: 25613729
DOI: 10.1038/emm.2014.82 -
FEBS Letters Dec 2010During the last three decades, a number of B-lymphocyte specific surface antigens have been defined some of which may also show activation/differentiation specific... (Review)
Review
During the last three decades, a number of B-lymphocyte specific surface antigens have been defined some of which may also show activation/differentiation specific expression. Here, we review the various signaling events and the receptor-ligand interactions for B-cell development, activation and differentiation. Our discussion and presentation include reviewing the in vivo and in vitro mechanisms. Focus is on the experiments that give us valuable insights into the B cell signaling mechanisms in vitro. Three significant pathways in B-cell development - c-Kit, FLT-3 and IL-7 signaling pathways are elucidated upon. Both antigen dependent and antigen independent mechanisms of B cell stimulation are also reviewed.
Topics: Animals; B-Lymphocytes; Cell Differentiation; Cell Proliferation; Humans; Lymphocyte Activation; Receptors, Immunologic; Signal Transduction
PubMed: 20728444
DOI: 10.1016/j.febslet.2010.08.022