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  1. Article ; Online: The unique biology of germinal center B cells.

    Young, Clara / Brink, Robert

    Immunity

    2021  Volume 54, Issue 8, Page(s) 1652–1664

    Abstract: Germinal center (GC) B cells are the source of the high-affinity, class-switched antibodies required for protective immunity. The unique biology of GC B cells involves iterative rounds of antibody gene somatic hypermutation coupled to multiple selection ... ...

    Abstract Germinal center (GC) B cells are the source of the high-affinity, class-switched antibodies required for protective immunity. The unique biology of GC B cells involves iterative rounds of antibody gene somatic hypermutation coupled to multiple selection and differentiation pathways. Recent advances in areas such as single cell and gene editing technologies have shed new light upon these complex and dynamic processes. We review these findings here and integrate them into the current understanding of GC B cell replication and death, the retention of high-affinity and class-switched B cells in the GC, and differentiation into plasma and memory cell effectors. We also discuss how the biology of GC responses relates to vaccine effectiveness and outline current and future challenges in the field.
    MeSH term(s) Antibody Affinity/immunology ; B-Lymphocytes/immunology ; Cell Differentiation/immunology ; Cell Proliferation ; Germinal Center/cytology ; Germinal Center/immunology ; Humans ; Immunoglobulin Class Switching/immunology ; Immunologic Memory/immunology ; Somatic Hypermutation, Immunoglobulin/immunology ; Vaccination
    Language English
    Publishing date 2021-08-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2021.07.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: B cells in the balance: Offsetting self-reactivity avoidance with protection against foreign.

    Young, Clara / Lau, Angelica W Y / Burnett, Deborah L

    Frontiers in immunology

    2022  Volume 13, Page(s) 951385

    Abstract: Antibodies are theoretically limitless in their diversity and specificity to foreign antigens; however they are constrained by the need to avoid binding to self. Germinal centers (GC) allow diversification and maturation of the antibody response towards ... ...

    Abstract Antibodies are theoretically limitless in their diversity and specificity to foreign antigens; however they are constrained by the need to avoid binding to self. Germinal centers (GC) allow diversification and maturation of the antibody response towards the foreign antigen. While self-tolerance mechanisms controlling self-reactivity during B cell maturation are well recognized, the mechanisms by which GCs balance self-tolerance and foreign binding especially in the face of cross-reactivity between self and foreign, remain much less well defined. In this review we explore the extent to which GC self-tolerance restricts affinity maturation. We present studies suggesting that the outcome is situationally dependent, affected by affinity and avidity to self-antigen, and the extent to which self-binding and foreign-binding are interdependent. While auto-reactive GC B cells can mutate away from self while maturing towards the foreign antigen, if no mutational trajectories allow for self-reactive redemption, self-tolerance prevails and GC responses to the foreign pathogen are restricted, except when self-tolerance checkpoints are relaxed. Finally, we consider whether polyreactivity is subject to the same level of restriction in GC responses, especially if polyreactivity is linked to an increase in foreign protection, as occurs in certain broadly neutralizing antibodies. Overall, the outcomes for GC B cells that bind self-antigen can range from redemption, transient relaxation in self-tolerance or restriction of the antibody response to the foreign pathogen.
    MeSH term(s) Autoantigens ; B-Lymphocytes ; Germinal Center ; Immune Tolerance ; Self Tolerance
    Chemical Substances Autoantigens
    Language English
    Publishing date 2022-07-25
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.951385
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Germinal centers and autoantibodies.

    Young, Clara / Brink, Robert

    Immunology and cell biology

    2020  Volume 98, Issue 6, Page(s) 480–489

    Abstract: Preventing self-reactive lymphocytes from participating in effector responses is fundamental to maintaining immunological self-tolerance and circumventing autoimmunity. A range of complementary mechanisms are known to act upon the primary B- and T-cell ... ...

    Abstract Preventing self-reactive lymphocytes from participating in effector responses is fundamental to maintaining immunological self-tolerance and circumventing autoimmunity. A range of complementary mechanisms are known to act upon the primary B- and T-cell repertoires to this effect, eliminating or silencing lymphocytes expressing self-reactive antigen receptors generated through V(D)J recombination in early lymphoid precursors. In the case of B cells, secondary diversification of antigen receptor repertoire by somatic hypermutation (SHM) provides an additional challenge, especially because this occurs in germinal center (GC) B cells that are actively responding to antigen and primed for differentiation into antibody-producing plasma cells. While it is clear that self-tolerance mechanisms do act to prevent antibody production by self-reactive GC B cells, it is also apparent that most pathogenic autoantibodies carry somatic mutations and so have derived from a GC response. Recent advances in the analysis of autoantibody-producing cells associated with human autoimmune diseases together with insights gained from animal models have increased our understanding of the relationships between GCs, SHM and autoantibody production. Here we discuss these developments and focus in particular on how they have illuminated the genesis and pathogenesis of one archetypal autoantibody, rheumatoid factor.
    MeSH term(s) Animals ; Autoantibodies/immunology ; Autoimmunity ; B-Lymphocytes/immunology ; Germinal Center/immunology ; Humans ; Rheumatoid Factor ; Self Tolerance
    Chemical Substances Autoantibodies ; Rheumatoid Factor (9009-79-4)
    Language English
    Publishing date 2020-03-18
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1111/imcb.12321
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  4. Article ; Online: Response to Cookstove Trials and Tribulations: What Is Needed to Decrease the Burden of Household Air Pollution?

    Gray, Cindy M / Colarte, Emily / Young, Clara

    Annals of the American Thoracic Society

    2018  Volume 15, Issue 8, Page(s) 1001

    MeSH term(s) Air Pollution ; Air Pollution, Indoor
    Language English
    Publishing date 2018-06-19
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.201804-254LE
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    Zs.A 5828: Show issues Location:
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  5. Article ; Online: Positive selection of IgG

    Sundling, Christopher / Lau, Angelica W Y / Bourne, Katherine / Young, Clara / Laurianto, Candy / Hermes, Jana R / Menzies, Rosemary J / Butt, Danyal / Kräutler, Nike J / Zahra, David / Suan, Dan / Brink, Robert

    Immunity

    2021  Volume 54, Issue 5, Page(s) 988–1001.e5

    Abstract: Positive selection of high-affinity B cells within germinal centers (GCs) drives affinity maturation of antibody responses. Here, we examined the mechanism underlying the parallel transition from immunoglobulin M (IgM) to IgG. Early GCs contained mostly ... ...

    Abstract Positive selection of high-affinity B cells within germinal centers (GCs) drives affinity maturation of antibody responses. Here, we examined the mechanism underlying the parallel transition from immunoglobulin M (IgM) to IgG. Early GCs contained mostly unswitched IgM
    MeSH term(s) Animals ; Antibody Formation/immunology ; Antigens/immunology ; B-Lymphocytes/immunology ; Female ; Germinal Center/immunology ; Immunoglobulin Class Switching/immunology ; Immunoglobulin G/immunology ; Immunoglobulin M/immunology ; Immunoglobulin Variable Region/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Sheep/immunology ; Somatic Hypermutation, Immunoglobulin/immunology
    Chemical Substances Antigens ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulin Variable Region
    Language English
    Publishing date 2021-04-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2021.03.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book: Medical specialty terminology / 2

    Young, Clara G. / Barger, James D.

    1972  

    Author's details Clara Gene Young ; James D. Barger
    Collection Medical specialty terminology
    Keywords Zahnpflege ; Hygiene ; Zahnmedizin
    Subject Odontologie ; Zahn-, Mund- und Kieferheilkunde ; Zahn-Mund-Kieferheilkunde ; Zahnheilkunde ; Gesundheitspflege ; Mundpflege ; Zähneputzen ; Mundhygiene ; Zahnhygiene ; Dental Hygiene
    Language English
    Size IX, 283 S. : Ill.
    Publisher Mosby
    Publishing place Saint Louis
    Publishing country United States
    Document type Book
    HBZ-ID HT013868677
    ISBN 0-8016-5661-3 ; 978-0-8016-5661-3
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    1997 A 9293 order for loan Magazin

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  7. Book: Medical specialty terminology / 1

    Young, Clara G. / Barger, James D.

    1971  

    Author's details Clara Gene Young ; James D. Barger
    Collection Medical specialty terminology
    Language English
    Size VII, 251 S. : Ill.
    Publisher Mosby
    Publishing place Saint Louis
    Publishing country United States
    Document type Book
    HBZ-ID HT002001449
    ISBN 0-8016-5660-5 ; 978-0-8016-5660-6
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
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  9. Article ; Online: CCR6 Defines Memory B Cell Precursors in Mouse and Human Germinal Centers, Revealing Light-Zone Location and Predominant Low Antigen Affinity.

    Suan, Dan / Kräutler, Nike J / Maag, Jesper L V / Butt, Danyal / Bourne, Katherine / Hermes, Jana R / Avery, Danielle T / Young, Clara / Statham, Aaron / Elliott, Michael / Dinger, Marcel E / Basten, Antony / Tangye, Stuart G / Brink, Robert

    Immunity

    2017  Volume 47, Issue 6, Page(s) 1142–1153.e4

    Abstract: Memory B cells (MBCs) and plasma cells (PCs) constitute the two cellular outputs of germinal center (GC) responses that together facilitate long-term humoral immunity. Although expression of the transcription factor BLIMP-1 identifies cells undergoing PC ...

    Abstract Memory B cells (MBCs) and plasma cells (PCs) constitute the two cellular outputs of germinal center (GC) responses that together facilitate long-term humoral immunity. Although expression of the transcription factor BLIMP-1 identifies cells undergoing PC differentiation, no such marker exists for cells committed to the MBC lineage. Here, we report that the chemokine receptor CCR6 uniquely marks MBC precursors in both mouse and human GCs. CCR6
    MeSH term(s) Animals ; B7-2 Antigen/genetics ; B7-2 Antigen/immunology ; Cell Differentiation ; Cell Lineage/immunology ; Gene Expression Profiling ; Gene Expression Regulation ; Germinal Center/cytology ; Germinal Center/immunology ; Humans ; Immunity, Humoral ; Immunologic Memory ; Immunophenotyping ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Phenotype ; Plasma Cells/cytology ; Plasma Cells/immunology ; Positive Regulatory Domain I-Binding Factor 1/genetics ; Positive Regulatory Domain I-Binding Factor 1/immunology ; Precursor Cells, B-Lymphoid/cytology ; Precursor Cells, B-Lymphoid/immunology ; Receptors, CCR6/genetics ; Receptors, CCR6/immunology ; Receptors, CXCR4/genetics ; Receptors, CXCR4/immunology ; Signal Transduction
    Chemical Substances B7-2 Antigen ; CCR6 protein, mouse ; CXCR4 protein, mouse ; Cd86 protein, mouse ; Prdm1 protein, mouse ; Receptors, CCR6 ; Receptors, CXCR4 ; Positive Regulatory Domain I-Binding Factor 1 (EC 2.1.1.-)
    Language English
    Publishing date 2017--19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2017.11.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: IgD attenuates the IgM-induced anergy response in transitional and mature B cells.

    Sabouri, Zahra / Perotti, Samuel / Spierings, Emily / Humburg, Peter / Yabas, Mehmet / Bergmann, Hannes / Horikawa, Keisuke / Roots, Carla / Lambe, Samantha / Young, Clara / Andrews, T Dan / Field, Matthew / Enders, Anselm / Reed, Joanne H / Goodnow, Christopher C

    Nature communications

    2016  Volume 7, Page(s) 13381

    Abstract: Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, ... ...

    Abstract Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, comprising 220 induced sequences including a core set of 97. Failure to co-express IgD with IgM decreases overall expression of receptors for self-antigen, but paradoxically increases the core anergy response, exemplified by increased Sdc1 encoding the cell surface marker syndecan-1. IgD expressed on its own is nevertheless competent to induce calcium signalling and the core anergy mRNA response. Syndecan-1 induction correlates with reduction of surface IgM and is exaggerated without surface IgD in many transitional and mature B cells. These results show that IgD attenuates the response to self-antigen in anergic cells and promotes their accumulation. In this way, IgD minimizes tolerance-induced holes in the pre-immune antibody repertoire.
    MeSH term(s) Animals ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Calcium Signaling/genetics ; Calcium Signaling/immunology ; Clonal Anergy/genetics ; Clonal Anergy/immunology ; Gene Expression Profiling/methods ; Immunoglobulin D/genetics ; Immunoglobulin D/immunology ; Immunoglobulin M/genetics ; Immunoglobulin M/immunology ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Male ; Mice, Inbred C57BL ; Mutation ; Receptors, Antigen, B-Cell/genetics ; Receptors, Antigen, B-Cell/immunology ; Receptors, Antigen, B-Cell/metabolism ; Self Tolerance/genetics ; Self Tolerance/immunology ; Syndecan-1/genetics ; Syndecan-1/immunology ; Syndecan-1/metabolism
    Chemical Substances Immunoglobulin D ; Immunoglobulin M ; Receptors, Antigen, B-Cell ; Sdc1 protein, mouse ; Syndecan-1
    Language English
    Publishing date 2016-11-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2041-1723
    ISSN (online) 2041-1723
    DOI 10.1038/ncomms13381
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