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  1. Article ; Online: BCR signaling is required for posttransplant lymphoproliferative disease in immunodeficient mice receiving human B cells.

    Zhang, Ting-Ting / Cheng, Rene Yu-Hong / Ott, Andee R / Dahl, Noelle P / Suchland, Emmaline R / Stoffers, Claire M / Asher, Gregory D / Hou, Deyin / Thouvenel, Christopher D / Hill, Tyler F / Rawlings, David J / James, Richard G

    Science translational medicine

    2024  Volume 16, Issue 742, Page(s) eadh8846

    Abstract: Posttransplant lymphoproliferative disease (PTLD) is a major therapeutic challenge that has been difficult to study using human cells because of a lack of suitable models for mechanistic characterization. Here, we show that ex vivo-differentiated B cells ...

    Abstract Posttransplant lymphoproliferative disease (PTLD) is a major therapeutic challenge that has been difficult to study using human cells because of a lack of suitable models for mechanistic characterization. Here, we show that ex vivo-differentiated B cells isolated from a subset of healthy donors can elicit pathologies similar to PTLD when transferred into immunodeficient mice. The primary driver of PTLD-like pathologies were IgM-producing plasmablasts with Epstein-Barr virus (EBV) genomes that expressed genes commonly associated with EBV latency. We show that a small subset of EBV
    MeSH term(s) Humans ; Animals ; Mice ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/therapy ; Herpesvirus 4, Human ; Lymphoproliferative Disorders/therapy ; Signal Transduction ; B-Lymphocytes
    Language English
    Publishing date 2024-04-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.adh8846
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6941: Show issues Location:
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  2. Article ; Online: SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells.

    Cheng, Rene Yu-Hong / de Rutte, Joseph / Ito, Cade Ellis K / Ott, Andee R / Bosler, Lucie / Kuo, Wei-Ying / Liang, Jesse / Hall, Brian E / Rawlings, David J / Di Carlo, Dino / James, Richard G

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 3567

    Abstract: The secreted products of cells drive many functions in vivo; however, methods to link this functional information to surface markers and transcriptomes have been lacking. By accumulating secretions close to secreting cells held within cavity-containing ... ...

    Abstract The secreted products of cells drive many functions in vivo; however, methods to link this functional information to surface markers and transcriptomes have been lacking. By accumulating secretions close to secreting cells held within cavity-containing hydrogel nanovials, we demonstrate workflows to analyze the amount of IgG secreted from single human B cells and link this information to surface markers and transcriptomes from the same cells. Measurements using flow cytometry and imaging flow cytometry corroborate the association between IgG secretion and CD38/CD138. By using oligonucleotide-labeled antibodies we find that upregulation of pathways for protein localization to the endoplasmic reticulum and mitochondrial oxidative phosphorylation are most associated with high IgG secretion, and uncover surrogate plasma cell surface markers (e.g., CD59) defined by the ability to secrete IgG. Altogether, this method links quantity of secretion with single-cell sequencing (SEC-seq) and enables researchers to fully explore the links between genome and function, laying the foundation for discoveries in immunology, stem cell biology, and beyond.
    MeSH term(s) Humans ; Plasma Cells ; B-Lymphocytes ; Cell Membrane ; Biomarkers/metabolism ; Immunoglobulin G/metabolism
    Chemical Substances Biomarkers ; Immunoglobulin G
    Language English
    Publishing date 2023-06-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-39367-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ex vivo engineered human plasma cells exhibit robust protein secretion and long-term engraftment in vivo.

    Cheng, Rene Yu-Hong / Hung, King L / Zhang, Tingting / Stoffers, Claire M / Ott, Andee R / Suchland, Emmaline R / Camp, Nathan D / Khan, Iram F / Singh, Swati / Yang, Ying-Jen / Rawlings, David J / James, Richard G

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 6110

    Abstract: Due to their unique longevity and capacity to secrete high levels of protein, plasma B cells have the potential to be used as a cell therapy for protein replacement. Here, we show that ex vivo engineered human plasma cells exhibit single-cell RNA ... ...

    Abstract Due to their unique longevity and capacity to secrete high levels of protein, plasma B cells have the potential to be used as a cell therapy for protein replacement. Here, we show that ex vivo engineered human plasma cells exhibit single-cell RNA profiles, scanning electron micrograph ultrastructural features, and in vivo homing capacity of long-lived plasma cells. After transferring human plasma cells to immunodeficient mice in the presence of the human cytokines BAFF and IL-6, we observe increases in retention of plasma cells in the bone marrow, with engraftment exceeding a year. The most profound in vivo effects of human IL-6 are observed within 20 days of transfer and could be explained by decreased apoptosis in newly differentiated plasma cells. Collectively, these results show that ex vivo engineered and differentiated human plasma cells have the potential for long-lived in vivo protein secretion, which can be modeled in small animals.
    MeSH term(s) Animals ; Blood Proteins ; Cytokines/metabolism ; Hematopoietic Stem Cell Transplantation ; Humans ; Interleukin-6 ; Mice ; Mice, SCID ; Plasma Cells/metabolism ; RNA
    Chemical Substances Blood Proteins ; Cytokines ; Interleukin-6 ; RNA (63231-63-0)
    Language English
    Publishing date 2022-10-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-33787-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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