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Frontiers in Immunology 2023Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of clonal plasma cells in the bone marrow (BM). It is known that early genetic... (Review)
Review
Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of clonal plasma cells in the bone marrow (BM). It is known that early genetic mutations in post-germinal center B/plasma cells are the cause of myelomagenesis. The acquisition of additional chromosomal abnormalities and distinct mutations further promote the outgrowth of malignant plasma cell populations that are resistant to conventional treatments, finally resulting in relapsed and therapy-refractory terminal stages of MM. In addition, myeloma cells are supported by autocrine signaling pathways and the tumor microenvironment (TME), which consists of diverse cell types such as stromal cells, immune cells, and components of the extracellular matrix. The TME provides essential signals and stimuli that induce proliferation and/or prevent apoptosis. In particular, the molecular pathways by which MM cells interact with the TME are crucial for the development of MM. To generate successful therapies and prevent MM recurrence, a thorough understanding of the molecular mechanisms that drive MM progression and therapy resistance is essential. In this review, we summarize key mechanisms that promote myelomagenesis and drive the clonal expansion in the course of MM progression such as autocrine signaling cascades, as well as direct and indirect interactions between the TME and malignant plasma cells. In addition, we highlight drug-resistance mechanisms and emerging therapies that are currently tested in clinical trials to overcome therapy-refractory MM stages.
Topics: Humans; Multiple Myeloma; Plasma Cells; Bone Marrow; Hematologic Neoplasms; Clonal Evolution; Tumor Microenvironment
PubMed: 37744361
DOI: 10.3389/fimmu.2023.1243997 -
Ear, Nose, & Throat Journal Jul 2020
Topics: Cheek; Diagnosis, Differential; Female; Humans; Medical Illustration; Middle Aged; Mucositis; Palate, Soft; Pharyngeal Diseases; Pharynx; Plasma Cells; Singing
PubMed: 31072192
DOI: 10.1177/0145561319849001 -
The Canadian Veterinary Journal = La... May 2022
Topics: Animals; Cat Diseases; Cats; Dermatitis; Foot Diseases; Plasma Cells
PubMed: 35502252
DOI: No ID Found -
Cell Reports Aug 2018Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. Using fluorescent glucose analog uptake, we defined multiple...
Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. Using fluorescent glucose analog uptake, we defined multiple developmentally independent mouse plasma cell populations with varying lifespans. Long-lived plasma cells imported more fluorescent glucose analog, expressed higher surface levels of the amino acid transporter CD98, and had more autophagosome mass than did short-lived cells. Low amino acid concentrations triggered reductions in both antibody secretion and mitochondrial respiration, especially by short-lived plasma cells. To explain these observations, we found that glutamine was used for both mitochondrial respiration and anaplerotic reactions, yielding glutamate and aspartate for antibody synthesis. Endoplasmic reticulum (ER) stress responses, which link metabolism to transcriptional outcomes, were similar between long- and short-lived subsets. Accordingly, population and single-cell transcriptional comparisons across mouse and human plasma cell subsets revealed few consistent and conserved differences. Thus, plasma cell antibody secretion and lifespan are primarily defined by non-transcriptional metabolic traits.
Topics: Humans; Longevity; Plasma Cells
PubMed: 30157439
DOI: 10.1016/j.celrep.2018.07.084 -
Frontiers in Immunology 2023Memory B cells and antibody-secreting cells are the two prime effector B cell populations that drive infection- and vaccine-induced long-term antibody-mediated immunity.... (Review)
Review
Memory B cells and antibody-secreting cells are the two prime effector B cell populations that drive infection- and vaccine-induced long-term antibody-mediated immunity. The antibody-mediated immunity mostly relies on the formation of specialized structures within secondary lymphoid organs, called germinal centers (GCs), that facilitate the interactions between B cells, T cells, and antigen-presenting cells. Antigen-activated B cells may proliferate and differentiate into GC-independent plasmablasts and memory B cells or differentiate into GC B cells. The GC B cells undergo proliferation coupled to somatic hypermutation of their immunoglobulin genes for antibody affinity maturation. Subsequently, affinity mature GC B cells differentiate into GC-dependent plasma cells and memory B cells. Here, we review how the NFκB signaling system controls B cell proliferation and the generation of GC B cells, plasmablasts/plasma cells, and memory B cells. We also identify and discuss some important unanswered questions in this connection.
Topics: Plasma Cells; B-Lymphocyte Subsets; Memory B Cells; B-Lymphocytes; Germinal Center
PubMed: 38169968
DOI: 10.3389/fimmu.2023.1185597 -
Current Oncology (Toronto, Ont.) Apr 2022Multiple myeloma is an incurable malignancy that initiates from a bone marrow resident clonal plasma cell and acquires successive mutational changes and genomic...
Multiple myeloma is an incurable malignancy that initiates from a bone marrow resident clonal plasma cell and acquires successive mutational changes and genomic alterations, eventually resulting in tumor burden accumulation and end-organ damage. It has been recently recognized that myeloma secondary genomic events result in extensive sub-clonal heterogeneity both in localized bone marrow areas and circulating peripheral blood plasma cells. Rare genomic subclones, including myeloma initiating cells, could be the drivers of disease progression and recurrence. Additionally, evaluation of rare myeloma cells in blood for disease monitoring has numerous advantages over invasive bone marrow biopsies. To this end, an unbiased method for detecting rare cells and delineating their genomic makeup enables disease detection and monitoring in conditions with low abundant cancer cells. In this study, we applied an enrichment-free four-plex (CD138, CD56, CD45, DAPI) immunofluorescence assay and single-cell DNA sequencing for morphogenomic characterization of plasma cells to detect and delineate common and rare plasma cells and discriminate between normal and malignant plasma cells in paired blood and bone marrow aspirates from five patients with newly diagnosed myeloma ( = 4) and monoclonal gammopathy of undetermined significance (n = 1). Morphological analysis confirms CD138+CD56+ cells in the peripheral blood carry genomic alterations that are clonally identical to those in the bone marrow. A subset of altered CD138+CD56- cells are also found in the peripheral blood consistent with the known variability in CD56 expression as a marker of plasma cell malignancy. Bone marrow tumor clinical cytogenetics is highly correlated with the single-cell copy number alterations of the liquid biopsy rare cells. A subset of rare cells harbors genetic alterations not detected by standard clinical diagnostic methods of random localized bone marrow biopsies. This enrichment-free morphogenomic approach detects and characterizes rare cell populations derived from the liquid biopsies that are consistent with clinical diagnosis and have the potential to extend our understanding of subclonality at the single-cell level in this disease. Assay validation in larger patient cohorts has the potential to offer liquid biopsy for disease monitoring with similar or improved disease detection as traditional blind bone marrow biopsies.
Topics: Bone Marrow; Clone Cells; Disease Progression; Humans; Multiple Myeloma; Plasma Cells
PubMed: 35621632
DOI: 10.3390/curroncol29050242 -
Cancer Cell Nov 2015Multiple myeloma (MM) is a plasma cell malignancy characterized by a heterogeneous clinical presentation. Genetic abnormalities are not only key events in the origin and...
Multiple myeloma (MM) is a plasma cell malignancy characterized by a heterogeneous clinical presentation. Genetic abnormalities are not only key events in the origin and progression of the disease but are also useful tools for prognosis, risk stratification, and therapeutic decision making. Although still incurable, a revolution in the treatment of MM is currently ongoing, leading to a significant improvement of clinical outcome and survival. To view this SnapShot, open or download the PDF.
Topics: Chromosome Aberrations; Female; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Male; Multiple Myeloma; Mutation; Plasma Cells; Prognosis; Signal Transduction; Survival Analysis
PubMed: 26555176
DOI: 10.1016/j.ccell.2015.10.014 -
Pathologica Jun 2019Russell body gastritis is caused by an accumulation of plasma cells within the gastric mucosa. These plasma cells are characterized by eosinophilic cytoplasmic...
Russell body gastritis is caused by an accumulation of plasma cells within the gastric mucosa. These plasma cells are characterized by eosinophilic cytoplasmic inclusions of immunoglobulin which are called "Russell bodies". We report a case of Russell body gastritis in a 28-year-old male who presented with abdominal pain and rectal bleeding. Endoscopy showed erosions with edema and vascular congestion in the gastric body and antrum. The biopsy showed chronic gastritis with plasma cell infiltration of the lamina propria. Many plasma cells contained cytoplasmic Russell bodies which stained positive for CD138, CD79a, Kappa and lambda light chains. The Russell bodies were negative for pancytokeratin, excluding signet ring cell carcinoma. Russell body gastritis is an uncommon, benign reactive condition.
Topics: Adult; Gastric Mucosa; Gastritis; Humans; Inclusion Bodies; Male; Plasma Cells
PubMed: 31388200
DOI: 10.32074/1591-951X-17-19 -
Frontiers in Immunology 2021Antibody-secreting cells (ASC), plasmablasts and plasma cells, are terminally differentiated B cells responsible for large-scale production and secretion of antibodies.... (Review)
Review
Antibody-secreting cells (ASC), plasmablasts and plasma cells, are terminally differentiated B cells responsible for large-scale production and secretion of antibodies. ASC are derived from activated B cells, which may differentiate extrafollicularly or form germinal center (GC) reactions within secondary lymphoid organs. ASC therefore consist of short-lived, poorly matured plasmablasts that generally secrete lower-affinity antibodies, or long-lived, highly matured plasma cells that generally secrete higher-affinity antibodies. The ASC population is responsible for producing an immediate humoral B cell response, the polyclonal antibody repertoire, as well as in parallel building effective humoral memory and immunity, or potentially driving pathology in the case of autoimmunity. ASC are phenotypically and transcriptionally distinct from other B cells and further distinguishable by morphology, varied lifespans, and anatomical localization. Single cell analyses are required to interrogate the functional and transcriptional diversity of ASC and their secreted antibody repertoire and understand the contribution of individual ASC responses to the polyclonal humoral response. Here we summarize the current and emerging functional and molecular techniques for high-throughput characterization of ASC with single cell resolution, including flow and mass cytometry, spot-based and microfluidic-based assays, focusing on functional approaches of the secreted antibodies: specificity, affinity, and secretion rate.
Topics: Animals; Antibody Formation; Antibody-Producing Cells; B-Lymphocytes; Gene Expression Profiling; Germinal Center; High-Throughput Screening Assays; Humans; Immunoassay; Plasma Cells; Single-Cell Analysis
PubMed: 35173713
DOI: 10.3389/fimmu.2021.821729 -
Cells Jun 2022Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D),...
Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations.
Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.
Topics: Diarrhea; Glycocalyx; Humans; Intestinal Mucosa; Irritable Bowel Syndrome; Nerve Fibers; Plasma Cells
PubMed: 35805133
DOI: 10.3390/cells11132046