title: Differential induction of plasma cells by isoforms of human TACI.
abstract: Subjects with common variable immune deficiency may have mutations in transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI). Unlike the murine gene, human TACI undergoes alternative messenger (m)RNA splicing to produce isoforms with 1 or 2 ligand-binding domains. Because both isoforms are found in human B cells, we compared their functions in transduced murine B and human pre-B cells. Although murine cells and pre-B cells transduced with the long TACI isoform retained surface CD19 and immunoglobulin G, cells transduced with the short TACI isoform completely lost these B-cell characteristics. Expression of the short TACI isoform produced intense nuclear factor κB activation, nuclear p65 translocation, and colocalization with myeloid differentiation factor 88 and calcium-modulating cyclophilin ligand. The short TACI-transduced cells became larger and CD138 positive, demonstrated upregulated BLIMP1 and XBP1 mRNA, and acquired the morphology of plasma cells. In contrast, cells bearing the long isoform had significantly less BLIMP1 and XBP1 mRNA and, for human pre-B cells, remained CD138 negative. Although human B cells express both isoforms, the short isoform predominates in CD27(+) B cells, toll-like receptor 9-activated peripheral B cells, and splenic marginal zone B cells. Although the transcriptional controls for alternative splicing of isoforms remain unknown, differential signals via isoforms may control plasma-cell generation in humans.
authors: Immunology Institute, and.
authors: Yolanda
authors: Y
authors: Garcia-Carmona
authors: Immunology Institute, and.
authors: Montserrat
authors: M
authors: Cols
authors: Immunology Institute, and.
authors: Adrian T
authors: AT
authors: Ting
authors: Immunology Institute, and.
authors: Lin
authors: L
authors: Radigan
authors: Fishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY;
authors: Frank J
authors: FJ
authors: Yuk
authors: Immunology Institute, and.
authors: Li
authors: L
authors: Zhang
authors: Immunology Institute, and Department of Immunology, Vall d'Hebron University Hospital, Barcelona, Spain; and.
authors: Andrea
authors: A
authors: Cerutti
authors: Immunology Institute, and Departments of Medicine and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Charlotte
authors: C
authors: Cunningham-Rundles
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D017074:Common Variable Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014161:Transduction, Genetic; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C089404:CAMLG protein, human; D004268:DNA-Binding Proteins; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D020033:Protein Isoforms; C498143:RELA protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; C108467:TNFRSF13B protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D053303:Transmembrane Activator and CAML Interactor Protein; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1
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