Abstract
Human plasma cells (PCs) and their precursors play an essential role in humoral immune response but are rare and difficult to harvest. We report the generation of human syndecan-1(+) and immunoglobulin secreting PCs starting from memory B cells in a 3-step and 10-day (D) culture, including a 6-fold cell amplification. We report the detailed phenotypic and Affymetrix gene expression profiles of these in vitro PCs as well as of intermediate cells (activated B cells and plasmablasts) compared with memory B cells and bone marrow PCs, which is accessible through an open web ATLAS (http://amazonia.transcriptome.eu/). We show this B cell-to-PC differentiation to involve IRF4 and AICDA expressions in D4 activated B cells, decrease of PAX5 and BCL6 expressions, and increase in PRDM1 and XBP1 expressions in D7 plasmablasts and D10 PCs. It involves down-regulation of genes controlled by Pax5 and induction of genes controlled by Blimp-1 and XBP1 (unfold protein response). The detailed phenotype of D10 PCs resembles that of peripheral blood PCs detected after immunization of healthy donors. This in vitro model will facilitate further studies in PC biology. It will likewise be helpful to study PC dyscrasias, including multiple myeloma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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B-Lymphocytes / cytology*
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Cell Culture Techniques
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Cell Differentiation*
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Cells, Cultured
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Cytidine Deaminase / genetics
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DNA-Binding Proteins / genetics
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Flow Cytometry
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Gene Expression Profiling
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Humans
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Immunoglobulins / metabolism
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Immunologic Memory
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Immunophenotyping
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Interferon Regulatory Factors / genetics
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Models, Biological
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Oligonucleotide Array Sequence Analysis / methods
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PAX5 Transcription Factor / genetics
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Plasma Cells / cytology*
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Plasma Cells / immunology
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Plasma Cells / metabolism
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Proto-Oncogene Proteins c-bcl-6
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Regulatory Factor X Transcription Factors
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Reverse Transcriptase Polymerase Chain Reaction
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Stem Cells / cytology*
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Stem Cells / immunology
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Stem Cells / metabolism
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Syndecan-1 / metabolism
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Time Factors
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Transcription Factors / genetics
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X-Box Binding Protein 1
Substances
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BCL6 protein, human
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DNA-Binding Proteins
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Immunoglobulins
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Interferon Regulatory Factors
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PAX5 Transcription Factor
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PAX5 protein, human
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Proto-Oncogene Proteins c-bcl-6
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Regulatory Factor X Transcription Factors
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Syndecan-1
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Transcription Factors
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X-Box Binding Protein 1
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XBP1 protein, human
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interferon regulatory factor-4
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase