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  1. Article ; Online: How I started a journal for postdoctoral researchers.

    van den Broek, Theo

    Nature

    2020  

    Language English
    Publishing date 2020-12-10
    Publishing country England
    Document type News
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-020-03498-5
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    Zs.A 26: Show issues Location:
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  2. Article ; Online: Prepare PhD holders for different career tracks.

    van den Broek, Theo / Prakken, Berent / Miedema, Frank

    Nature

    2021  Volume 600, Issue 7889, Page(s) 386

    MeSH term(s) Career Choice ; Education, Graduate ; Occupations
    Language English
    Publishing date 2021-12-16
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-021-03695-w
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  3. Article ; Online: Invasion of spontaneous germinal centers by naive B cells is rapid and persistent.

    van den Broek, Theo / Oleinika, Kristine / Rahmayanti, Siti / Castrillon, Carlos / van der Poel, Cees E / Carroll, Michael C

    Science immunology

    2024  Volume 9, Issue 93, Page(s) eadi8150

    Abstract: In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for ... ...

    Abstract In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions to limit autoimmune pathologies, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs by wild-type B cells required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a tool for identifying early events in the breaking of B cell tolerance in autoimmunity.
    MeSH term(s) Mice ; Animals ; B-Lymphocytes ; Germinal Center ; Autoimmunity ; Lupus Erythematosus, Systemic ; Epitopes
    Chemical Substances Epitopes
    Language English
    Publishing date 2024-03-22
    Publishing country United States
    Document type Journal Article
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.adi8150
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Coronavirus: postdoc winners need paid extensions.

    van den Broek, Theo / Gould, James

    Nature

    2020  Volume 583, Issue 7816, Page(s) 360

    MeSH term(s) Coronavirus Infections ; Humans ; Middle East Respiratory Syndrome Coronavirus
    Keywords covid19
    Language English
    Publishing date 2020-07-14
    Publishing country England
    Document type Letter
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-020-02087-w
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  6. Article ; Online: Complex subsets but redundant clonality after B cells egress from spontaneous germinal centers.

    Castrillon, Carlos / Simoni, Lea / van den Broek, Theo / van der Poel, Cees / Akama-Garren, Elliot H / Ma, Minghe / Carroll, Michael C

    eLife

    2023  Volume 12

    Abstract: Affinity matured self-reactive antibodies are found in autoimmune diseases like systemic lupus erythematous. Here, we used fate-mapping reporter mice and single-cell transcriptomics coupled to antibody repertoire analysis to characterize the post- ... ...

    Abstract Affinity matured self-reactive antibodies are found in autoimmune diseases like systemic lupus erythematous. Here, we used fate-mapping reporter mice and single-cell transcriptomics coupled to antibody repertoire analysis to characterize the post-germinal center (GC) B cell compartment in a new mouse model of autoimmunity. Antibody-secreting cells (ASCs) and memory B cells (MemBs) from spontaneous GCs grouped into multiple subclusters. ASCs matured into two terminal clusters, with distinct secretion, antibody repertoire and metabolic profiles. MemBs contained FCRL5+ and CD23+ subsets, with different in vivo localization in the spleen. GC-derived FCRL5+ MemBs share transcriptomic and repertoire properties with atypical B cells found in aging and infection and localize to the marginal zone, suggesting a similar contribution to recall responses. While transcriptomically diverse, ASC and MemB subsets maintained an underlying clonal redundancy. Therefore, self-reactive clones could escape subset-targeting therapy by perpetuation of self-reactivity in distinct subsets.
    MeSH term(s) Mice ; Animals ; B-Lymphocytes ; Germinal Center ; Autoimmunity ; Autoimmune Diseases ; Autoantibodies
    Chemical Substances Autoantibodies
    Language English
    Publishing date 2023-06-21
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.81012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The full spectrum of human naive T cells.

    van den Broek, Theo / Borghans, José A M / van Wijk, Femke

    Nature reviews. Immunology

    2018  Volume 18, Issue 6, Page(s) 363–373

    Abstract: Naive T cells have long been regarded as a developmentally synchronized and fairly homogeneous and quiescent cell population, the size of which depends on age, thymic output and prior infections. However, there is increasing evidence that naive T cells ... ...

    Abstract Naive T cells have long been regarded as a developmentally synchronized and fairly homogeneous and quiescent cell population, the size of which depends on age, thymic output and prior infections. However, there is increasing evidence that naive T cells are heterogeneous in phenotype, function, dynamics and differentiation status. Current strategies to identify naive T cells should be adjusted to take this heterogeneity into account. Here, we provide an integrated, revised view of the naive T cell compartment and discuss its implications for healthy ageing, neonatal immunity and T cell reconstitution following haematopoietic stem cell transplantation.
    MeSH term(s) Adaptive Immunity ; Adult ; Antigens, CD/metabolism ; Cell Differentiation/immunology ; Cell Movement/immunology ; Healthy Aging/immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunity, Innate ; Infant, Newborn ; Models, Immunological ; T-Lymphocyte Subsets/cytology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Thymus Gland/cytology ; Thymus Gland/immunology ; Tissue Distribution
    Chemical Substances Antigens, CD
    Language English
    Publishing date 2018-03-09
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-018-0001-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5565: Show issues Location:
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  8. Article ; Online: Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease.

    Akama-Garren, Elliot H / van den Broek, Theo / Simoni, Lea / Castrillon, Carlos / van der Poel, Cees E / Carroll, Michael C

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 6687

    Abstract: Pathogenic autoantibodies contribute to tissue damage and clinical decline in autoimmune disease. Follicular T cells are central regulators of germinal centers, although their contribution to autoantibody-mediated disease remains unclear. Here we perform ...

    Abstract Pathogenic autoantibodies contribute to tissue damage and clinical decline in autoimmune disease. Follicular T cells are central regulators of germinal centers, although their contribution to autoantibody-mediated disease remains unclear. Here we perform single cell RNA and T cell receptor (TCR) sequencing of follicular T cells in a mouse model of autoantibody-mediated disease, allowing for analyses of paired transcriptomes and unbiased TCRαβ repertoires at single cell resolution. A minority of clonotypes are preferentially shared amongst autoimmune follicular T cells and clonotypic expansion is associated with differential gene signatures in autoimmune disease. Antigen prediction using algorithmic and machine learning approaches indicates convergence towards shared specificities between non-autoimmune and autoimmune follicular T cells. However, differential autoimmune transcriptional signatures are preserved even amongst follicular T cells with shared predicted specificities. These results demonstrate that follicular T cells are phenotypically distinct in B cell-driven autoimmune disease, providing potential therapeutic targets to modulate autoantibody development.
    MeSH term(s) Animals ; Autoimmune Diseases/genetics ; Autoimmune Diseases/immunology ; Autoimmune Diseases/metabolism ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Cells, Cultured ; Clone Cells/immunology ; Clone Cells/metabolism ; Gene Expression Profiling/methods ; Germinal Center/cytology ; Germinal Center/immunology ; Germinal Center/metabolism ; Mice, Inbred C57BL ; Microscopy, Confocal ; RNA-Seq/methods ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Single-Cell Analysis/methods ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; Mice
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2021-11-18
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-27035-8
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  9. Article ; Online: Complex subsets but redundant clonality after B cells egress from spontaneous germinal centers

    Carlos Castrillon / Lea Simoni / Theo van den Broek / Cees van der Poel / Elliot H Akama-Garren / Minghe Ma / Michael C Carroll

    eLife, Vol

    2023  Volume 12

    Abstract: Affinity matured self-reactive antibodies are found in autoimmune diseases like systemic lupus erythematous. Here, we used fate-mapping reporter mice and single-cell transcriptomics coupled to antibody repertoire analysis to characterize the post- ... ...

    Abstract Affinity matured self-reactive antibodies are found in autoimmune diseases like systemic lupus erythematous. Here, we used fate-mapping reporter mice and single-cell transcriptomics coupled to antibody repertoire analysis to characterize the post-germinal center (GC) B cell compartment in a new mouse model of autoimmunity. Antibody-secreting cells (ASCs) and memory B cells (MemBs) from spontaneous GCs grouped into multiple subclusters. ASCs matured into two terminal clusters, with distinct secretion, antibody repertoire and metabolic profiles. MemBs contained FCRL5+ and CD23+ subsets, with different in vivo localization in the spleen. GC-derived FCRL5+ MemBs share transcriptomic and repertoire properties with atypical B cells found in aging and infection and localize to the marginal zone, suggesting a similar contribution to recall responses. While transcriptomically diverse, ASC and MemB subsets maintained an underlying clonal redundancy. Therefore, self-reactive clones could escape subset-targeting therapy by perpetuation of self-reactivity in distinct subsets.
    Keywords autoimmunity ; memory B cell ; antibody-secreting cell ; single-cell sequencing ; B cell receptor repertoire ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease

    Elliot H. Akama-Garren / Theo van den Broek / Lea Simoni / Carlos Castrillon / Cees E. van der Poel / Michael C. Carroll

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 19

    Abstract: Follicular T cells regulate germinal centre reactions, but their phenotypes in autoimmune disease are unclear. Using a mouse model of autoantibody disease, the authors show that autoimmune follicular T cells differ by TCR clonotype and transcriptional ... ...

    Abstract Follicular T cells regulate germinal centre reactions, but their phenotypes in autoimmune disease are unclear. Using a mouse model of autoantibody disease, the authors show that autoimmune follicular T cells differ by TCR clonotype and transcriptional profile from non-autoimmune follicular T cells.
    Keywords Science ; Q
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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