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  1. Article ; Online: mTECs Aire on the side of caution.

    Bortnick, Alexandra / Murre, Cornelis

    Nature immunology

    2018  Volume 19, Issue 2, Page(s) 100–101

    MeSH term(s) Cell Differentiation ; Chromatin ; Gene Expression Regulation ; Immune Tolerance
    Chemical Substances Chromatin
    Language English
    Publishing date 2018-01-18
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-017-0033-7
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  2. Article ; Online: Nuclear morphology is shaped by loop-extrusion programs.

    Patta, Indumathi / Zand, Maryam / Lee, Lindsay / Mishra, Shreya / Bortnick, Alexandra / Lu, Hanbin / Prusty, Arpita / McArdle, Sara / Mikulski, Zbigniew / Wang, Huan-You / Cheng, Christine S / Fisch, Kathleen M / Hu, Ming / Murre, Cornelis

    Nature

    2024  Volume 627, Issue 8002, Page(s) 196–203

    Abstract: It is well established that neutrophils adopt malleable polymorphonuclear shapes to migrate through narrow interstitial tissue ... ...

    Abstract It is well established that neutrophils adopt malleable polymorphonuclear shapes to migrate through narrow interstitial tissue spaces
    MeSH term(s) Cell Cycle Checkpoints ; Cell Cycle Proteins/deficiency ; Cell Cycle Proteins/metabolism ; Cell Movement ; Chromatin/chemistry ; Chromatin/metabolism ; Chromosomes/chemistry ; Chromosomes/metabolism ; Neutrophils/cytology ; Neutrophils/metabolism ; Cell Nucleus Shape ; Nucleic Acid Conformation ; Cell Differentiation/genetics ; Inflammation/genetics ; Enhancer Elements, Genetic ; Cell Lineage/genetics
    Chemical Substances Cell Cycle Proteins ; Chromatin
    Language English
    Publishing date 2024-02-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-024-07086-9
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  3. Article ; Online: Cellular and chromatin dynamics of antibody-secreting plasma cells.

    Bortnick, Alexandra / Murre, Cornelis

    Wiley interdisciplinary reviews. Developmental biology

    2016  Volume 5, Issue 2, Page(s) 136–149

    Abstract: Plasma cells are terminally differentiated B cells responsible for maintaining protective serum antibody titers. Despite their clinical importance, our understanding of the linear genomic features and chromatin structure of plasma cells is incomplete. ... ...

    Abstract Plasma cells are terminally differentiated B cells responsible for maintaining protective serum antibody titers. Despite their clinical importance, our understanding of the linear genomic features and chromatin structure of plasma cells is incomplete. The plasma cell differentiation program can be triggered by different signals and in multiple, diverse peripheral B cell subsets. This heterogeneity raises questions about the gene regulatory circuits required for plasma cell specification. Recently, new regulators of plasma cell differentiation have been identified and the enhancer landscapes of naïve B cells have been described. Other studies have revealed that the bone marrow niche harbors heterogeneous plasma cell subsets. Still undefined are the minimal requirements to become a plasma cell and what molecular features make peripheral B cell subsets competent to become antibody-secreting plasma cells. New technologies promise to reveal underlying chromatin configurations that promote efficient antibody secretion. For further resources related to this article, please visit the WIREs website.
    MeSH term(s) Animals ; B-Lymphocyte Subsets/cytology ; B-Lymphocyte Subsets/immunology ; B-Lymphocyte Subsets/metabolism ; Cell Differentiation ; Chromatin Assembly and Disassembly ; Gene Regulatory Networks ; Humans
    Language English
    Publishing date 2016-03
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1759-7692
    ISSN (online) 1759-7692
    DOI 10.1002/wdev.213
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  4. Article ; Online: mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion.

    Gaudette, Brian T / Jones, Derek D / Bortnick, Alexandra / Argon, Yair / Allman, David

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 723

    Abstract: How activated B cells build biosynthetic pathways and organelle structures necessary for subsequent robust antibody secretion is still unclear. The dominant model holds that nascent plasma cells adapt to increased antibody synthesis by activating the ... ...

    Abstract How activated B cells build biosynthetic pathways and organelle structures necessary for subsequent robust antibody secretion is still unclear. The dominant model holds that nascent plasma cells adapt to increased antibody synthesis by activating the unfolded protein response (UPR) under the control of the transcription factor Xbp1. Here, by analyzing gene expression in activated B cells with or without plasma cell-inductive signals, we find that follicular B cells up-regulate a wide array of UPR-affiliated genes before initiating antibody secretion; furthermore, initial transcription of these loci requires the mTORC1 kinase adaptor, Raptor, but not Xbp1. Transcriptomic analyses of resting marginal zone B cells, which generate plasma cells with exceptionally rapid kinetics, reinforce these results by revealing the basal expression of UPR-affiliated mRNA networks without detectable Xbp1 activity. We thus conclude that B cells utilize mTORC1 to prepare for subsequent plasma cell function, before the onset of antibody synthesis.
    MeSH term(s) Animals ; Antibodies/metabolism ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; B-Lymphocytes/physiology ; Cell Differentiation ; Gene Expression Regulation ; Lipopolysaccharides/pharmacology ; Lymphocyte Activation ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation ; Regulatory-Associated Protein of mTOR/genetics ; Regulatory-Associated Protein of mTOR/metabolism ; Spleen/cytology ; Unfolded Protein Response/genetics ; Unfolded Protein Response/physiology ; X-Box Binding Protein 1/genetics ; X-Box Binding Protein 1/metabolism
    Chemical Substances Antibodies ; Lipopolysaccharides ; Regulatory-Associated Protein of mTOR ; Rptor protein, mouse ; X-Box Binding Protein 1 ; Xbp1 protein, mouse ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
    Language English
    Publishing date 2020-02-05
    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/s41467-019-14032-1
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  5. Article ; Online: No strict requirement for eosinophils for bone marrow plasma cell survival.

    Bortnick, Alexandra / Chernova, Irene / Spencer, Sean P / Allman, David

    European journal of immunology

    2018  Volume 48, Issue 5, Page(s) 815–821

    Abstract: Lasting antibody responses are maintained by long-lived plasma cells, which are thought to lodge in the BM in specialized survival niches. Eosinophils have been reported to function as a critical component of the BM survival niche where they are thought ... ...

    Abstract Lasting antibody responses are maintained by long-lived plasma cells, which are thought to lodge in the BM in specialized survival niches. Eosinophils have been reported to function as a critical component of the BM survival niche where they are thought to provide pro-survival signals to nearby plasma cells. Recent study shows that many BM plasma cells are recently generated and chiefly short-lived cells, raising the possibility that rare plasma cell-eosinophil interactions are a rate-limiting step needed to establish lasting humoral immunity. To address these issues, we examined the impact of eosinophil depletion on short- and long-lived BM plasma cells in the context of antibody responses induced by both T-cell dependent and T-cell independent antigens. Surprisingly, our results failed to support a role for eosinophils in either plasma cell generation or survival. These studies included examination of plasma cell frequencies in mice lacking eosinophils either after antibody-mediated depletion, or due to mutation of the GATA1 locus.
    MeSH term(s) Animals ; Antibodies/immunology ; Antibody Formation/immunology ; Bone Marrow/immunology ; Bone Marrow Cells/immunology ; Eosinophils/immunology ; Female ; GATA1 Transcription Factor/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plasma Cells/cytology ; Plasma Cells/immunology ; T-Lymphocytes/immunology ; Tumor Necrosis Factor Ligand Superfamily Member 13/metabolism
    Chemical Substances Antibodies ; GATA1 Transcription Factor ; Gata1 protein, mouse ; Tnfsf13 protein, mouse ; Tumor Necrosis Factor Ligand Superfamily Member 13
    Language English
    Publishing date 2018-03-23
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.201747229
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    Zs.A 489: Show issues Location:
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  6. Article ; Online: What is and what should always have been: long-lived plasma cells induced by T cell-independent antigens.

    Bortnick, Alexandra / Allman, David

    Journal of immunology (Baltimore, Md. : 1950)

    2013  Volume 190, Issue 12, Page(s) 5913–5918

    Abstract: It is well accepted that Ag-induced B cell differentiation often results in the generation of exceptionally long-lived plasma cells. Much of the work supporting this viewpoint stems from studies focused on germinal center-derived plasma cells secreting ... ...

    Abstract It is well accepted that Ag-induced B cell differentiation often results in the generation of exceptionally long-lived plasma cells. Much of the work supporting this viewpoint stems from studies focused on germinal center-derived plasma cells secreting high-affinity isotype-switched Abs in mice immunized with T cell-dependent Ags. In contrast, less attention has been devoted to understanding Ab responses to T cell-independent Ags and pathogens. In this study, we review recent work showing that T cell-independent Ags consisting of either polysaccharides or LPSs also induce the formation of long-lived plasma cells, despite their general inability to sustain germinal center responses. This new information provides a framework for more fully understanding the forces underlying immunity to pathogens that resist T cell recognition and the extracellular cues governing plasma cell longevity.
    MeSH term(s) Animals ; Antigens/immunology ; Cell Differentiation/immunology ; Humans ; Lymphocyte Activation/immunology ; Plasma Cells/cytology ; Plasma Cells/immunology ; T-Lymphocytes/immunology
    Chemical Substances Antigens
    Language English
    Publishing date 2013-06-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1300161
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  7. Article ; Online: A HESitant decision for T cells.

    Bortnick, Alexandra / Murre, Cornelis

    Nature immunology

    2013  Volume 14, Issue 12, Page(s) 1209–1210

    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/immunology ; CCAAT-Enhancer-Binding Protein-alpha/immunology ; Female ; Homeodomain Proteins/immunology ; Receptor, Notch1/immunology ; T-Lymphocytes/immunology ; Transcription Factor HES-1
    Chemical Substances Basic Helix-Loop-Helix Transcription Factors ; CCAAT-Enhancer-Binding Protein-alpha ; Hes1 protein, mouse ; Homeodomain Proteins ; Receptor, Notch1 ; Transcription Factor HES-1
    Language English
    Publishing date 2013-10-30
    Publishing country United States
    Document type News ; Comment
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/ni.2765
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  8. Article ; Online: A system-wide health sciences faculty mentor training program is associated with improved effective mentoring and institutional climate.

    Trejo, JoAnn / Wingard, Deborah / Hazen, Virginia / Bortnick, Alexandra / Van Hoesen, Karen / Byars-Winston, Angela / Pfund, Christine / Reznik, Vivian

    Journal of clinical and translational science

    2021  Volume 6, Issue 1, Page(s) e18

    Abstract: Introduction: Mentorship is critical for faculty success, satisfaction, and engagement. However, many faculty, particularly underrepresented racial/ethnic (UR) faculty, lack access to high-quality mentoring. In an effort to improve mentoring for all ... ...

    Abstract Introduction: Mentorship is critical for faculty success, satisfaction, and engagement. However, many faculty, particularly underrepresented racial/ethnic (UR) faculty, lack access to high-quality mentoring. In an effort to improve mentoring for all faculty, we developed and implemented a formally structured faculty mentor training program (FMTP) across UC San Diego Health Sciences, which included institutional support, mentorship training, and department/division mentorship programs.
    Methods: FMTP impact was evaluated using three primary outcome variables: mentoring quality, mentoring behaviors, and institutional climate. Participants' self-assessed mentoring competencies were measured using validated instruments.
    Results: A total of 391 (23%) of Health Sciences faculty participated in FMTP. Participation rate was higher for women than men (30% versus 17%) and highest for UR faculty (39%). FMTP was implemented in 16 of 19 departments. Self-reported mentoring improved for FMTP participants with mentoring quality (
    Conclusion: The implementation of a system-wide formal structured FMTP was associated with improved faculty satisfaction, quality of mentoring, and institutional climate, especially for UR faculty.
    Language English
    Publishing date 2021-12-23
    Publishing country England
    Document type Journal Article
    ISSN 2059-8661
    ISSN (online) 2059-8661
    DOI 10.1017/cts.2021.883
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  9. Article ; Online: AID targeting: old mysteries and new challenges.

    Chandra, Vivek / Bortnick, Alexandra / Murre, Cornelis

    Trends in immunology

    2015  Volume 36, Issue 9, Page(s) 527–535

    Abstract: Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and class-switch recombination. AID deamination is not exclusive to immunoglobulin loci; it ... ...

    Abstract Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and class-switch recombination. AID deamination is not exclusive to immunoglobulin loci; it can instigate DNA lesions in non-immunoglobulin genes and thus stringent checks are in place to constrain and restrict its activity. Recent findings have provided new insights into the mechanisms that target AID activity to specific genomic regions, revealing an involvement for noncoding RNAs associated with polymerase pausing and with enhancer transcription as well as genomic architecture. We review these findings and integrate them into a model for multilevel regulation of AID expression and targeting in immunoglobulin and non-immunoglobulin loci. Within this framework we discuss gaps in understanding, and outline important areas of further research.
    MeSH term(s) Animals ; Antibody Formation/genetics ; Antibody Formation/immunology ; Cytidine Deaminase/chemistry ; Cytidine Deaminase/genetics ; Cytidine Deaminase/metabolism ; Gene Expression Regulation ; Genetic Loci ; Humans ; Immunoglobulin Class Switching ; Immunoglobulins/genetics ; Protein Binding ; Protein Interaction Domains and Motifs ; Transcription Factors/metabolism
    Chemical Substances Immunoglobulins ; Transcription Factors ; AICDA (activation-induced cytidine deaminase) (EC 3.5.4.-) ; Cytidine Deaminase (EC 3.5.4.5)
    Language English
    Publishing date 2015-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2015.07.003
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  10. Article ; Online: Plasma Cell Fate Is Orchestrated by Elaborate Changes in Genome Compartmentalization and Inter-chromosomal Hubs.

    Bortnick, Alexandra / He, Zhaoren / Aubrey, Megan / Chandra, Vivek / Denholtz, Matthew / Chen, Kenian / Lin, Yin C / Murre, Cornelis

    Cell reports

    2020  Volume 31, Issue 13, Page(s) 107876

    Language English
    Publishing date 2020-06-24
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2020.107876
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