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  1. Article ; Online: Functional heterogeneity in the memory B-cell response.

    Henry, Brittany / Laidlaw, Brian J

    Current opinion in immunology

    2023  Volume 80, Page(s) 102281

    Abstract: Most vaccines induce robust antibody and memory B-cell (MBC) responses that are capable of mediating protective immunity. However, antibody titers wane following vaccination necessitating the administration of booster vaccines to maintain a protective ... ...

    Abstract Most vaccines induce robust antibody and memory B-cell (MBC) responses that are capable of mediating protective immunity. However, antibody titers wane following vaccination necessitating the administration of booster vaccines to maintain a protective antibody titer. MBCs are stably maintained following vaccination and can rapidly give rise to antibody-secreting cells or undergo further affinity maturation upon antigen re-encounter. Repeated antigen encounter results in the development of MBCs that encode antibodies capable of mediating broadly protective immunity against viruses such as SARS-CoV-2 and influenza. Here, we summarize emerging evidence that MBCs are a heterogeneous population composed of transcriptionally and phenotypically distinct subsets that have discrete roles in mediating protective immunity upon antigen re-encounter and examine the implications of these findings for the development of vaccines capable of eliciting broadly protective immunity.
    MeSH term(s) Humans ; B-Lymphocytes ; SARS-CoV-2 ; COVID-19 ; Influenza, Human ; Influenza Vaccines ; Antigens ; Vaccination ; Antibodies, Viral ; Immunologic Memory
    Chemical Substances Influenza Vaccines ; Antigens ; Antibodies, Viral
    Language English
    Publishing date 2023-01-16
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2022.102281
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Development and function of tissue-resident memory B cells.

    Chen, Changfeng / Laidlaw, Brian J

    Advances in immunology

    2022  Volume 155, Page(s) 1–38

    Abstract: Barrier tissues are the primary site of infection for pathogens likely to cause future pandemics. Tissue-resident lymphocytes can rapidly detect pathogens upon infection of barrier tissues and are critical in preventing viral spread. However, most ... ...

    Abstract Barrier tissues are the primary site of infection for pathogens likely to cause future pandemics. Tissue-resident lymphocytes can rapidly detect pathogens upon infection of barrier tissues and are critical in preventing viral spread. However, most vaccines fail to induce tissue-resident lymphocytes and are instead reliant on circulating antibodies to mediate protective immunity. Circulating antibody titers wane over time following vaccination leaving individuals susceptible to breakthrough infections by variant viral strains that evade antibody neutralization. Memory B cells were recently found to establish tissue residence following infection of barrier tissues. Here, we summarize emerging evidence for the importance of tissue-resident memory B cells in the establishment of protective immunity against viral and bacterial challenge. We also discuss the role of tissue-resident memory B cells in regulating the progression of non-infectious diseases. Finally, we examine new approaches to develop vaccines capable of eliciting barrier immunity.
    MeSH term(s) Humans ; Animals ; Immunologic Memory ; Memory B Cells ; Vaccination ; Vaccines
    Chemical Substances Vaccines
    Language English
    Publishing date 2022-10-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80226-8
    ISSN 1557-8445 ; 0065-2776
    ISSN (online) 1557-8445
    ISSN 0065-2776
    DOI 10.1016/bs.ai.2022.08.001
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  3. Article ; Online: The germinal centre B cell response to SARS-CoV-2.

    Laidlaw, Brian J / Ellebedy, Ali H

    Nature reviews. Immunology

    2021  Volume 22, Issue 1, Page(s) 7–18

    Abstract: The germinal centre (GC) response is critical for the generation of affinity-matured plasma cells and memory B cells capable of mediating long-term protective immunity. Understanding whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ... ...

    Abstract The germinal centre (GC) response is critical for the generation of affinity-matured plasma cells and memory B cells capable of mediating long-term protective immunity. Understanding whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination elicits a GC response has profound implications for the capacity of responding B cells to contribute to protection against infection. However, direct assessment of the GC response in humans remains a major challenge. Here we summarize emerging evidence for the importance of the GC response in the establishment of durable and broad immunity against SARS-CoV-2 and discuss new approaches to modulate the GC response to better protect against newly emerging SARS-CoV-2 variants. We also discuss new findings showing that the GC B cell response persists in the draining lymph nodes for at least 6 months in some individuals following vaccination with SARS-CoV-2 mRNA-based vaccines.
    MeSH term(s) Animals ; Antibodies, Viral/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19/virology ; COVID-19 Vaccines/immunology ; Germinal Center/immunology ; Humans ; Memory B Cells/immunology ; SARS-CoV-2/immunology ; mRNA Vaccines/immunology
    Chemical Substances Antibodies, Viral ; COVID-19 Vaccines ; mRNA Vaccines
    Language English
    Publishing date 2021-12-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-021-00657-1
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  4. Article ; Online: Transcriptional regulation of memory B cell differentiation.

    Laidlaw, Brian J / Cyster, Jason G

    Nature reviews. Immunology

    2020  Volume 21, Issue 4, Page(s) 209–220

    Abstract: Memory B cells (MBCs) are critical for the rapid development of protective immunity following re-infection. MBCs capable of neutralizing distinct subclasses of pathogens, such as influenza and HIV, have been identified in humans. However, efforts to ... ...

    Abstract Memory B cells (MBCs) are critical for the rapid development of protective immunity following re-infection. MBCs capable of neutralizing distinct subclasses of pathogens, such as influenza and HIV, have been identified in humans. However, efforts to develop vaccines that induce broadly protective MBCs to rapidly mutating pathogens have not yet been successful. Better understanding of the signals regulating MBC development and function are essential to overcome current challenges hindering successful vaccine development. Here, we discuss recent advancements regarding the signals and transcription factors regulating germinal centre-derived MBC development and function.
    MeSH term(s) B-Lymphocyte Subsets/immunology ; B-Lymphocytes/immunology ; CD40 Antigens ; Cell Differentiation/genetics ; Gene Expression Regulation ; Germinal Center/cytology ; Humans ; Immunologic Memory/genetics ; Immunologic Memory/immunology ; Precursor Cells, B-Lymphoid/immunology ; Proto-Oncogene Proteins c-bcl-6 ; Proto-Oncogene Proteins c-myc ; Receptors, Antigen, B-Cell ; STAT3 Transcription Factor ; STAT6 Transcription Factor ; Signal Transduction ; Toll-Like Receptors
    Chemical Substances CD40 Antigens ; Proto-Oncogene Proteins c-bcl-6 ; Proto-Oncogene Proteins c-myc ; Receptors, Antigen, B-Cell ; STAT3 Transcription Factor ; STAT6 Transcription Factor ; Toll-Like Receptors
    Keywords covid19
    Language English
    Publishing date 2020-10-06
    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/s41577-020-00446-2
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  5. Article ; Online: Interfer'n with antibody responses.

    Laidlaw, Brian J / Cyster, Jason G

    Science immunology

    2016  Volume 1, Issue 4

    Abstract: Type I interferon blocks the generation of neutralizing antibodies in response to chronic infection. ...

    Abstract Type I interferon blocks the generation of neutralizing antibodies in response to chronic infection.
    Language English
    Publishing date 2016-10-21
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.aaj1836
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  6. Article ; Online: The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development.

    Laidlaw, Brian J / Duan, Lihui / Xu, Ying / Vazquez, Sara E / Cyster, Jason G

    Nature immunology

    2020  Volume 21, Issue 9, Page(s) 1082–1093

    Abstract: Memory B cells (MBCs) are essential for long-lived humoral immunity. However, the transcription factors involved in MBC differentiation are poorly defined. Here, using single-cell RNA sequencing analysis, we identified a population of germinal center (GC) ...

    Abstract Memory B cells (MBCs) are essential for long-lived humoral immunity. However, the transcription factors involved in MBC differentiation are poorly defined. Here, using single-cell RNA sequencing analysis, we identified a population of germinal center (GC) B cells in the process of differentiating into MBCs. Using an inducible CRISPR-Cas9 screening approach, we identified the hematopoietically expressed homeobox protein Hhex as a transcription factor regulating MBC differentiation. The corepressor Tle3 was also identified in the screen and was found to interact with Hhex to promote MBC development. Bcl-6 directly repressed Hhex in GC B cells. Reciprocally, Hhex-deficient MBCs exhibited increased Bcl6 expression and reduced expression of the Bcl-6 target gene Bcl2. Overexpression of Bcl-2 was able to rescue MBC differentiation in Hhex-deficient cells. We also identified Ski as an Hhex-induced transcription factor involved in MBC differentiation. These findings establish an important role for Hhex-Tle3 in regulating the transcriptional circuitry governing MBC differentiation.
    MeSH term(s) Animals ; B-Lymphocyte Subsets/immunology ; B-Lymphocytes/immunology ; CRISPR-Cas Systems ; Cell Differentiation ; Co-Repressor Proteins/genetics ; Co-Repressor Proteins/metabolism ; Female ; Gene Expression Regulation ; Germinal Center/immunology ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Immunologic Memory ; Lymphocyte Activation ; Male ; Mice ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-bcl-6/genetics ; Proto-Oncogene Proteins c-bcl-6/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Co-Repressor Proteins ; Hhex protein, mouse ; Homeodomain Proteins ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogene Proteins c-bcl-6 ; Tle3 protein, mouse ; Transcription Factors
    Language English
    Publishing date 2020-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-020-0713-6
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  7. Article ; Online: CD62L expression marks a functionally distinct subset of memory B cells.

    Hanson, Christopher H / Henry, Brittany / Andhare, Pradhnesh / Lin, Frank J / Pak, Haley / Turner, Jackson S / Adams, Lucas J / Liu, Tom / Fremont, Daved H / Ellebedy, Ali H / Laidlaw, Brian J

    Cell reports

    2023  Volume 42, Issue 12, Page(s) 113542

    Abstract: The memory B cell response consists of phenotypically distinct subsets that differ in their ability to respond upon antigen re-encounter. However, the pathways regulating the development and function of memory B cell subsets are poorly understood. Here, ... ...

    Abstract The memory B cell response consists of phenotypically distinct subsets that differ in their ability to respond upon antigen re-encounter. However, the pathways regulating the development and function of memory B cell subsets are poorly understood. Here, we show that CD62L and CD44 are progressively expressed on mouse memory B cells and identify transcriptionally and functionally distinct memory B cell subsets. Bcl6 is important in regulating memory B cell subset differentiation with overexpression of Bcl6 resulting in impaired CD62L
    MeSH term(s) Animals ; Humans ; Mice ; Antigens/metabolism ; Immunologic Memory ; Lymphocyte Activation ; Memory B Cells ; T-Lymphocyte Subsets/metabolism ; Vaccination
    Chemical Substances Antigens ; SELL protein, human
    Language English
    Publishing date 2023-12-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.113542
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  8. Article ; Online: The multifaceted role of CD4(+) T cells in CD8(+) T cell memory.

    Laidlaw, Brian J / Craft, Joseph E / Kaech, Susan M

    Nature reviews. Immunology

    2016  Volume 16, Issue 2, Page(s) 102–111

    Abstract: Following infection, T cells differentiate into a heterogeneous population of effector T cells that can mediate pathogen clearance. A subset of these effector T cells possesses the ability to survive long term and mature into memory T cells that can ... ...

    Abstract Following infection, T cells differentiate into a heterogeneous population of effector T cells that can mediate pathogen clearance. A subset of these effector T cells possesses the ability to survive long term and mature into memory T cells that can provide long-term immunity. Understanding the signals that regulate the development of memory T cells is crucial to efforts to design vaccines capable of eliciting T cell-based immunity. CD4(+) T cells are essential in the formation of protective memory CD8(+) T cells following infection or immunization. However, until recently, the mechanisms by which CD4(+) T cells act to support memory CD8(+) T cell development following infection were unclear. Here, we discuss recent studies that provide insight into the multifaceted role of CD4(+) T cells in the regulation of memory CD8(+) T cell differentiation.
    MeSH term(s) CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Humans ; Immunization ; Immunologic Memory/immunology ; Infection/immunology ; Vaccination
    Language English
    Publishing date 2016-01-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/nri.2015.10
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  9. Article ; Online: Sphingosine-1-phosphate receptor 2 restrains egress of γδ T cells from the skin.

    Laidlaw, Brian J / Gray, Elizabeth E / Zhang, Yang / Ramírez-Valle, Francisco / Cyster, Jason G

    The Journal of experimental medicine

    2019  Volume 216, Issue 7, Page(s) 1487–1496

    Abstract: Maintenance of a population of IL-17-committed γδ T cells in the dermis is important in promoting tissue immunity. However, the signals facilitating γδ T cell retention within the dermis remain poorly understood. Here, we find that sphingosine-1- ... ...

    Abstract Maintenance of a population of IL-17-committed γδ T cells in the dermis is important in promoting tissue immunity. However, the signals facilitating γδ T cell retention within the dermis remain poorly understood. Here, we find that sphingosine-1-phosphate receptor 2 (S1PR2) acts in a cell-intrinsic manner to oppose γδ T cell migration from the dermis to the skin draining lymph node (dLN). Migration of dermal γδ T cells to the dLN under steady-state conditions occurs in an S1PR1-dependent manner. S1PR1 and CD69 are reciprocally expressed on dermal γδ T cells, with loss of CD69 associated with increased S1PR1 expression and enhanced migration to the dLN. γδ T cells lacking both S1PR2 and CD69 are impaired in their maintenance within the dermis. These findings provide a mechanism for how IL-17
    MeSH term(s) Animals ; Cell Movement ; Flow Cytometry ; Mice ; Mice, Inbred C57BL ; Real-Time Polymerase Chain Reaction ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Receptors, CCR6/metabolism ; Receptors, CCR6/physiology ; Skin/cytology ; Skin/immunology ; Skin/metabolism ; Sphingosine-1-Phosphate Receptors/metabolism ; Sphingosine-1-Phosphate Receptors/physiology
    Chemical Substances CCR6 protein, mouse ; Receptors, Antigen, T-Cell, gamma-delta ; Receptors, CCR6 ; Sphingosine-1-Phosphate Receptors ; sphingosine-1-phosphate receptor-2, mouse
    Language English
    Publishing date 2019-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20190114
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  10. Article ; Online: Development of Tbet- and CD11c-expressing B cells in a viral infection requires T follicular helper cells outside of germinal centers.

    Song, Wenzhi / Antao, Olivia Q / Condiff, Emily / Sanchez, Gina M / Chernova, Irene / Zembrzuski, Krzysztof / Steach, Holly / Rubtsova, Kira / Angeletti, Davide / Lemenze, Alexander / Laidlaw, Brian J / Craft, Joe / Weinstein, Jason S

    Immunity

    2022  Volume 55, Issue 2, Page(s) 290–307.e5

    Abstract: ... ...

    Abstract Tbet
    MeSH term(s) Animals ; Antibodies, Viral/metabolism ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; CD11 Antigens/metabolism ; Cell Differentiation/immunology ; Germinal Center/immunology ; Alphainfluenzavirus/immunology ; Integrins/metabolism ; Lymphocyte Subsets/immunology ; Lymphocyte Subsets/metabolism ; Lymphocytic choriomeningitis virus/immunology ; Memory B Cells/immunology ; Memory B Cells/metabolism ; Mice ; Spleen/immunology ; T Follicular Helper Cells/immunology ; T-Box Domain Proteins/metabolism ; Virus Diseases/immunology
    Chemical Substances Antibodies, Viral ; CD11 Antigens ; Integrins ; Itgax protein, mouse ; T-Box Domain Proteins
    Language English
    Publishing date 2022-01-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.2022.01.002
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