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Immunological Reviews Sep 2010Plasma cells have long been recognized as the basis of humoral immunity, yet we are only now beginning to appreciate the complexities of plasma cell development and the... (Review)
Review
Plasma cells have long been recognized as the basis of humoral immunity, yet we are only now beginning to appreciate the complexities of plasma cell development and the fact that not all plasma cells are created equal. In vivo, plasma cells can arise from two developmental routes: one occurring outside the follicle and another within the germinal center. A B cell's decision to follow one of these pathways is in part determined by the phenotypic subset to which it belongs and is also influenced by the nature of the antigen eliciting the response and the affinity of the B-cell receptor for that antigen. Once a plasma cell has chosen one of these pathways, the outcome of differentiation is relatively hard-wired. However, the phenotype of the plasma cells arising from these two pathways is distinct in terms of survival, location, and the quantity and quality of antibody they secrete. The extra-follicular pathway represents a relatively unchecked route to differentiation resulting in the generation of short-lived plasma cells that secrete low-affinity antibody. The germinal center response, however, allows the integration of external signals to delay plasma cell differentiation, eventually generating a plasma cell that secretes high-affinity antibody of an appropriate class, and that persists for a lifetime. The means by which these varying properties are conferred to a developing plasma cell are the subject of intense investigation.
Topics: Animals; B-Lymphocyte Subsets; Cell Differentiation; Cell Survival; Humans; Plasma Cells
PubMed: 20727034
DOI: 10.1111/j.1600-065X.2010.00940.x -
Blood Jun 2022
Topics: Humans; Leukemia, Plasma Cell; Plasma Cells
PubMed: 35737405
DOI: 10.1182/blood.2022016032 -
Current Opinion in Immunology Apr 2008Humoral immunity depends on the regulated production and maintenance of antibody secreting cells during the course of an immune response. Recent insights into the... (Review)
Review
Humoral immunity depends on the regulated production and maintenance of antibody secreting cells during the course of an immune response. Recent insights into the transcriptional regulation of the initiation of plasma cell differentiation have clarified aspects of this process, particularly with respect to the choice between the memory B cell and plasma cell differentiation pathways. It is now possible to specify the conditions favouring these outcomes and to predict where they might occur within the germinal center. Once formed, plasma cell survival is critically dependent on accessing niches that are formed by stomal elements in both normal and inflamed tissues. The apparent homeostasis of plasma cell numbers means that new specificities can persist only at the expense of existing ones, raising questions on how immunological memory is maintained in the face of new immune responses. The answer appears to be through the reduction of the process to a single cell level, thereby introducing an element of stochasticity.
Topics: Cell Differentiation; Cell Survival; DNA-Binding Proteins; Germinal Center; Humans; Plasma Cells; Proto-Oncogene Proteins c-bcl-6
PubMed: 18456483
DOI: 10.1016/j.coi.2008.03.016 -
Immunological Reviews Sep 2021
Topics: Plasma Cells
PubMed: 34396544
DOI: 10.1111/imr.13017 -
Hematology/oncology Clinics of North... Dec 2020Immunoglobulin light chain amyloidosis is the most common systemic amyloidosis. The pathogenetic mechanism is deposition of fibrils of misfolded immunoglobulin free... (Review)
Review
Immunoglobulin light chain amyloidosis is the most common systemic amyloidosis. The pathogenetic mechanism is deposition of fibrils of misfolded immunoglobulin free light chains, more often lambda, typically produced by clonal plasma cells. Distinct Ig light chain variable region genotypes underlie most light chain amyloidosis and dictate tissue tropism. Light chain amyloidosis fibrils cause distortion of the histologic architecture and direct cytotoxicity, leading to rapidly progressive organ dysfunction and eventually patient demise. A high index of clinical suspicion with rapid tissue diagnosis and commencement of combinatorial, highly effective cytoreductive therapy is crucial to avoid irreversible organ damage and early mortality.
Topics: Amyloid; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Plasma Cells
PubMed: 33099420
DOI: 10.1016/j.hoc.2020.08.001 -
Current Opinion in Immunology Apr 2004Microarray analyses and gene targeting have recently enhanced the understanding of factors involved in normal plasma cells and multiple myeloma. Plasma cells develop... (Review)
Review
Microarray analyses and gene targeting have recently enhanced the understanding of factors involved in normal plasma cells and multiple myeloma. Plasma cells develop from marginal zone or germinal center B cells following stimulation by antigen, microbial products, TNF family signals and cytokines. Transcription factors, B-lymphocyte-induced maturation protein 1 (Blimp-1) and X-box binding protein 1 (XBP-1) are required for plasma cell development. They regulate sets of genes that induce immunoglobulin secretion, halt proliferation and block alternative B-cell fates. In multiple myeloma, transforming events lead to proliferation and survival, but programs for plasma cell differentiation and the inhibition of B-cell genes appear to be largely intact.
Topics: Cell Differentiation; Gene Expression Regulation; Multiple Myeloma; Oligonucleotide Array Sequence Analysis; Plasma Cells; Receptors, Antigen, B-Cell; Signal Transduction; Transcription Factors
PubMed: 15023417
DOI: 10.1016/j.coi.2004.02.001 -
Journal of Clinical Immunology May 2016Autophagy is a highly conserved pathway that recycles cytosolic material and organelles via lysosomal degradation. Once simplistically viewed as a non-selective survival... (Review)
Review
Autophagy is a highly conserved pathway that recycles cytosolic material and organelles via lysosomal degradation. Once simplistically viewed as a non-selective survival strategy in dire straits, autophagy has emerged as a tightly regulated process ensuring organelle function, proteome plasticity, cell differentiation and tissue homeostasis, with key roles in physiology and disease. Selective target recognition, mediated by specific adapter proteins, enables autophagy to orchestrate highly specialized functions in innate and adaptive immunity. Among them, the shaping of plasma cells for sustainable antibody production through a negative control on their differentiation program. Moreover, memory B cells and long-lived plasma cells require autophagy to exist. Further, the plasma cell malignancy, multiple myeloma deploys abundant autophagy, essential for homeostasis, survival and drug resistance.
Topics: Animals; Autophagosomes; Autophagy; B-Lymphocytes; Carrier Proteins; Cell Transformation, Neoplastic; Humans; Immune System; Neoplasms, Plasma Cell; Plasma Cells; Protein Binding; Signal Transduction
PubMed: 26984755
DOI: 10.1007/s10875-016-0254-9 -
Trends in Immunology Jan 2018Humoral immunity is generated and maintained by antigen-specific antibodies that counter infectious pathogens. Plasma cells are the major producers of antibodies during... (Review)
Review
Humoral immunity is generated and maintained by antigen-specific antibodies that counter infectious pathogens. Plasma cells are the major producers of antibodies during and after infections, and each plasma cell produces some thousands of antibody molecules per second. This magnitude of secretion requires enormous quantities of amino acids and glycosylation sugars to properly build and fold antibodies, biosynthetic substrates to fuel endoplasmic reticulum (ER) biogenesis, and additional carbon sources to generate energy. Many of these processes are likely to be linked, thereby affording possibilities to improve vaccine design and to develop new therapies for autoimmunity. We review here aspects of plasma cell biology with an emphasis on recent studies and the relationships between intermediary metabolism, antibody production, and lifespan.
Topics: Animals; Antibodies; Antibody Formation; Cell Survival; Endoplasmic Reticulum; Humans; Immunity, Humoral; Plasma Cells; Protein Folding; Stress, Physiological
PubMed: 28919256
DOI: 10.1016/j.it.2017.08.007 -
Methods in Molecular Biology (Clifton,... 2017In germinal centers (GCs), B cells undergo repeated cycles of proliferation and affinity-based selection, and differentiate into memory B cells or long-lived plasma...
In germinal centers (GCs), B cells undergo repeated cycles of proliferation and affinity-based selection, and differentiate into memory B cells or long-lived plasma cells. It has been difficult to elucidate regulatory mechanisms for the dynamic GC B cell maturation and differentiation, partly because experimental manipulation of GC B cells has been limited. Here we describe a culture system in which we can induce massive expansion of naive B cells that exhibit GC B cell-like phenotype and acquire abilities to differentiate into memory B cells or bone marrow plasma cells depending on cytokine conditions. This system will allow us to elucidate the molecular mechanisms of GC B cell differentiation.
Topics: Animals; B-Lymphocytes; Biomarkers; Cell Culture Techniques; Cell Line; Cells, Cultured; Cytokines; Germinal Center; Immunologic Memory; Mice; Plasma Cells; Spleen
PubMed: 28589353
DOI: 10.1007/978-1-4939-7095-7_11 -
Immunological Reviews Aug 2003Cell-cycle control is a major determinant of homeostasis during B-cell development, differentiation, and tumorigenesis. The generation of an antibody response requires... (Review)
Review
Cell-cycle control is a major determinant of homeostasis during B-cell development, differentiation, and tumorigenesis. The generation of an antibody response requires activation and expansion of antigen-specific B cells and terminal differentiation of these cells into plasma cells. Plasma cells arrest in the G1 phase of the cell cycle, but the mechanism that underlies timely cell-cycle entry and exit in the humoral immune response is not known. The mammalian cell-cycle is regulated primarily at the G1 to S transition by the balance between positive regulators, the cyclin-dependent kinases (CDK) together with cyclins, and negative regulators, the CDK inhibitors. One such inhibitor, p18INK4c, has been shown to be required for cell-cycle termination and final differentiation of non-secreting plasmacytoid cells to antibody-secreting plasma cells. This finding provides the first direct evidence for cell-cycle control of B-cell immunity. It also raises important questions regarding cell-cycle control of cellular differentiation, apoptosis, and earlier steps of B-cell terminal differentiation. This article discusses the biochemical mechanism of cell-cycle control in the context of antibody response and plasma cell differentiation along with the role of cell-cycle dysregulation in the pathogenesis of multiple myeloma, the plasma cell cancer.
Topics: Animals; Cell Cycle; Cell Differentiation; Cell Transformation, Neoplastic; Humans; Multiple Myeloma; Plasma Cells
PubMed: 12846806
DOI: 10.1034/j.1600-065x.2003.00065.x