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  1. Article ; Online: Characterization and Activity of TIM-1 and IL-10-Reporter Expressing Regulatory B Cells.

    Mohib, Kanishka / Rothstein, David M / Ding, Qing

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2270, Page(s) 179–202

    Abstract: In addition to their role in humoral immunity, B cells can exhibit regulatory activity. Such B cells have been termed regulatory B cells (Bregs). Bregs have been shown to inhibit inflammatory immune responses in a variety of autoimmune, alloimmune, and ... ...

    Abstract In addition to their role in humoral immunity, B cells can exhibit regulatory activity. Such B cells have been termed regulatory B cells (Bregs). Bregs have been shown to inhibit inflammatory immune responses in a variety of autoimmune, alloimmune, and infectious settings. Breg activity is frequently IL-10-dependent, although a number of other mechanisms have been identified. However, our understanding of Bregs has been hampered by their rarity, lack of a specific phenotypic marker, and poor insight into their induction and maintenance. A variety of B-cell subsets enriched for IL-10
    MeSH term(s) Animals ; B-Lymphocytes/immunology ; B-Lymphocytes, Regulatory/immunology ; Flow Cytometry/methods ; Hepatitis A Virus Cellular Receptor 1/metabolism ; Interleukin-10/isolation & purification ; Interleukin-10/metabolism ; Lymphocyte Activation/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Signal Transduction
    Chemical Substances Hepatitis A Virus Cellular Receptor 1 ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2021-01-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1237-8_10
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  2. Article ; Online: Regulatory B cells: TIM-1, transplant tolerance, and rejection.

    Cherukuri, Aravind / Mohib, Kanishka / Rothstein, David M

    Immunological reviews

    2021  Volume 299, Issue 1, Page(s) 31–44

    Abstract: Regulatory B cells (Bregs) ameliorate autoimmune disease and prevent allograft rejection. Conversely, they hinder effective clearance of pathogens and malignancies. Breg activity is mainly attributed to IL-10 expression, but also utilizes additional ... ...

    Abstract Regulatory B cells (Bregs) ameliorate autoimmune disease and prevent allograft rejection. Conversely, they hinder effective clearance of pathogens and malignancies. Breg activity is mainly attributed to IL-10 expression, but also utilizes additional regulatory mechanisms such as TGF-β, FasL, IL-35, and TIGIT. Although Bregs are present in various subsets defined by phenotypic markers (including canonical B cell subsets), our understanding of Bregs has been limited by the lack of a broadly inclusive and specific phenotypic or transcriptional marker. TIM-1, a broad marker for Bregs first identified in transplant models, plays a major role in Breg maintenance and induction. Here, we expand on the role of TIM-1
    MeSH term(s) Animals ; Autoimmune Diseases ; B-Lymphocytes, Regulatory ; Immune Tolerance ; Mice ; Signal Transduction ; Transplantation Tolerance
    Language English
    Publishing date 2021-01-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.12933
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  3. Article ; Online: B Cell IL-4 Drives Th2 Responses

    Song, Zhixing / Yuan, Wenjia / Zheng, Leting / Wang, Xingan / Kuchroo, Vijay K / Mohib, Kanishka / Rothstein, David M

    Frontiers in immunology

    2022  Volume 13, Page(s) 762390

    Abstract: B cells can be polarized to express various cytokines. The roles of IFNγ and IL-10, expressed respectively by B effector 1 (Be1) and Bregs, have been established in pathogen clearance, tumor growth, autoimmunity and allograft rejection. However, ... ...

    Abstract B cells can be polarized to express various cytokines. The roles of IFNγ and IL-10, expressed respectively by B effector 1 (Be1) and Bregs, have been established in pathogen clearance, tumor growth, autoimmunity and allograft rejection. However, the
    MeSH term(s) Allografts ; Animals ; B-Lymphocytes, Regulatory ; Graft Rejection ; Hypersensitivity ; Interleukin-10 ; Interleukin-4/genetics ; Mice ; Mice, Inbred C57BL
    Chemical Substances Interleukin-10 (130068-27-8) ; Interleukin-4 (207137-56-2)
    Language English
    Publishing date 2022-03-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.762390
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  4. Article ; Online: Regulatory B cells and transplantation: almost prime time?

    Mohib, Kanishka / Cherukuri, Aravind / Rothstein, David M

    Current opinion in organ transplantation

    2017  Volume 23, Issue 5, Page(s) 524–532

    Abstract: Purpose of review: Regulatory B cells (Bregs) are potent inhibitors of the immune system with the capacity to suppress autoimmune and alloimmune responses. Murine transplant models showing that Bregs can promote allograft tolerance are now supported by ... ...

    Abstract Purpose of review: Regulatory B cells (Bregs) are potent inhibitors of the immune system with the capacity to suppress autoimmune and alloimmune responses. Murine transplant models showing that Bregs can promote allograft tolerance are now supported by clinical data showing that patients who develop operational tolerance have higher frequency of Bregs. Breg function has been widely studied resulting in improved understanding of their biology and effector mechanisms. However, our overall understanding of Bregs remains poor due the lack of specific marker, limited knowledge of how and where they act in vivo, and whether different Breg subpopulations exhibit different functions.
    Recent findings: In this review we detail murine and human phenotypic markers used to identify Bregs, their induction, maintenance, and mechanisms of immune suppression. We highlight recent advances in the field including their use as biomarkers to predict allograft rejection, in-vitro expansion of Bregs, and the effects of commonly used immunosuppressive drugs on their induction and frequency.
    Summary: Clinical data continue to emerge in support of Bregs playing an important role in preventing transplant rejection. Hence, it is necessary for the transplant field to better comprehend the mechanisms of Breg induction and approaches to preserve or even enhance their activity to improve long-term transplant outcomes.
    MeSH term(s) B-Lymphocytes, Regulatory/immunology ; Humans ; Transplantation/methods ; Transplantation Tolerance/genetics
    Language English
    Publishing date 2017-12-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1390429-2
    ISSN 1531-7013 ; 1087-2418
    ISSN (online) 1531-7013
    ISSN 1087-2418
    DOI 10.1097/MOT.0000000000000559
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  5. Article ; Online: IL-17-dependent fibroblastic reticular cell training boosts tissue protective mucosal immunity through IL-10-producing B cells.

    Wu, Dongwen / Poholek, Catherine H / Majumder, Saikat / Liu, Qixing / Revu, Shankar K / Mohib, Kanishka / Rothstein, David M / McGeachy, Mandy J

    Science immunology

    2021  Volume 6, Issue 66, Page(s) eaao3669

    Abstract: Prior experience of pathogen-associated stimuli reduces morbidity and mortality to newly encountered infections through innate immune training, which can be enhanced by childhood vaccination. Fibroblastic reticular cells (FRCs) are stromal cells in ... ...

    Abstract Prior experience of pathogen-associated stimuli reduces morbidity and mortality to newly encountered infections through innate immune training, which can be enhanced by childhood vaccination. Fibroblastic reticular cells (FRCs) are stromal cells in lymphoid organs that support lymphocyte localization and survival and modulate adaptive immune responses. IL-17 signaling is important for FRC metabolism and proliferation during inflammatory responses. Here, we show that FRC-intrinsic IL-17 signaling was required for protective antibody-mediated immunity to the gut bacterial pathogen
    MeSH term(s) Animals ; B-Lymphocytes/immunology ; Female ; Fibroblasts/immunology ; Immunity, Mucosal/immunology ; Interleukin-10/biosynthesis ; Interleukin-17/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic
    Chemical Substances IL10 protein, mouse ; Il17a protein, mouse ; Interleukin-17 ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2021-12-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.aao3669
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  6. Article ; Online: Antigen-dependent interactions between regulatory B cells and T cells at the T:B border inhibit subsequent T cell interactions with DCs.

    Mohib, Kanishka / Cherukuri, Aravind / Zhou, Yu / Ding, Qing / Watkins, Simon C / Rothstein, David M

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2019  Volume 20, Issue 1, Page(s) 52–63

    Abstract: IL-10+ regulatory B cells (Bregs) inhibit immune responses in various settings. While Bregs appear to inhibit inflammatory cytokine expression by CD4+ T cells and innate immune cells, their reported impact on CD8+ T cells is contradictory. Moreover, it ... ...

    Abstract IL-10+ regulatory B cells (Bregs) inhibit immune responses in various settings. While Bregs appear to inhibit inflammatory cytokine expression by CD4+ T cells and innate immune cells, their reported impact on CD8+ T cells is contradictory. Moreover, it remains unclear which effects of Bregs are direct versus indirect. Finally, the subanatomical localization of Breg suppressive function and the nature of their intercellular interactions remain unknown. Using novel tamoxifen-inducible B cell-specific IL-10 knockout mice, we found that Bregs inhibit CD8+ T cell proliferation and inhibit inflammatory cytokine expression by both CD4+ and CD8+ T cells. Sort-purified Bregs from IL-10-reporter mice were adoptively transferred into wild-type hosts and examined by live-cell imaging. Bregs localized to the T:B border, specifically entered the T cell zone, and made more frequent and longer contacts with both CD4+ and CD8+ T cells than did non-Bregs. These Breg:T cell interactions were antigen-specific and reduced subsequent T:DC contacts. Thus, Bregs inhibit T cells through direct cognate interactions that subsequently reduce DC:T cell interactions.
    MeSH term(s) Animals ; B-Lymphocytes, Regulatory/immunology ; B-Lymphocytes, Regulatory/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Communication ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Interleukin-10/physiology ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Interleukin-10/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism
    Chemical Substances IL10 protein, mouse ; Receptors, Interleukin-10 ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2019-08-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.15546
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    Zs.A 5542: Show issues Location:
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  7. Article ; Online: Differentiation and characterization of dendritic cells from human embryonic stem cells.

    Mohib, Kanishka / Wang, Lisheng

    Current protocols in immunology

    2012  Volume Chapter 22, Page(s) Unit 22F.11

    Abstract: Human embryonic stem cells (hESCs) offer great hope in regenerative medicine. Their ability to give rise to almost any type of cell present in the adult body makes them an invaluable tool in finding cures for a variety of diseases. While considerable ... ...

    Abstract Human embryonic stem cells (hESCs) offer great hope in regenerative medicine. Their ability to give rise to almost any type of cell present in the adult body makes them an invaluable tool in finding cures for a variety of diseases. While considerable protocols have been devised to efficiently differentiate hESCs into various cells types including cells of hematopoietic origin, this protocol will focus on the derivation of dendritic cells (DC), a potent antigen-presenting cell. DCs are a highly important arm of the immune system, as they represent one of the few cells that bridge the innate and adaptive systems, leading to effective pathogen clearance. The study of DCs has led to potential applications in diverse fields, such as vaccine development, tumor immunology, and transplantation. In this protocol, we describe two different methods of differentiating hESCs into DCs. The first method uses OP9 bone marrow stromal supporting cells as a coculture system, while the second method utilizes the formation of embryoid body (EB, cellular aggregate) as an approach. To assure the successful outcome and subsequent assessment of the differentiated DCs, supporting protocols have been included in this chapter.
    MeSH term(s) Adult ; Animals ; Antigens, CD/immunology ; Bone Marrow Cells/cytology ; Cell Culture Techniques/methods ; Cell Differentiation ; Cell Line ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/drug effects ; Embryonic Stem Cells/immunology ; Feeder Cells/cytology ; Fibroblasts/cytology ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Interleukin-4/pharmacology ; Mice ; Spheroids, Cellular/cytology ; Stromal Cells/cytology
    Chemical Substances Antigens, CD ; Interleukin-4 (207137-56-2) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
    Language English
    Publishing date 2012-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1934-368X
    ISSN (online) 1934-368X
    DOI 10.1002/0471142735.im22f11s98
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  8. Article ; Online: TIM-4 Identifies IFN-γ-Expressing Proinflammatory B Effector 1 Cells That Promote Tumor and Allograft Rejection.

    Ding, Qing / Mohib, Kanishka / Kuchroo, Vijay K / Rothstein, David M

    Journal of immunology (Baltimore, Md. : 1950)

    2017  Volume 199, Issue 7, Page(s) 2585–2595

    Abstract: B cells give rise to polarized subsets, including B effector 1 (Be1) cells and regulatory B cells, which can promote or inhibit immune responses through expression of IFN-γ and IL-10, respectively. Such subsets likely explain why B cell depletion can ... ...

    Abstract B cells give rise to polarized subsets, including B effector 1 (Be1) cells and regulatory B cells, which can promote or inhibit immune responses through expression of IFN-γ and IL-10, respectively. Such subsets likely explain why B cell depletion can either ameliorate or exacerbate inflammatory diseases; however, these cells remain poorly understood because of the absence of specific markers. Although T cell Ig and mucin domain-containing molecule (TIM)-1 broadly identifies IL-10
    MeSH term(s) Allografts/immunology ; Animals ; Antibodies, Monoclonal/administration & dosage ; B-Lymphocyte Subsets/immunology ; Cell Differentiation ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Graft Rejection ; Interferon-gamma/biosynthesis ; Interleukin-10/genetics ; Interleukin-10/immunology ; Interleukin-4/immunology ; Lymphocyte Activation ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology ; Membrane Proteins/genetics ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Mice ; Neoplasm Metastasis ; Th1 Cells/physiology ; Transplantation Tolerance
    Chemical Substances Antibodies, Monoclonal ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; Membrane Proteins ; TIM-4 protein, mouse ; Interleukin-10 (130068-27-8) ; Interleukin-4 (207137-56-2) ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2017-08-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    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.1602107
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    Ud II Zs.37: Show issues Location:
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  9. Article ; Online: Regulatory and Effector B Cells: A New Path Toward Biomarkers and Therapeutic Targets to Improve Transplant Outcomes?

    Cherukuri, Aravind / Ding, Qing / Sharma, Akhil / Mohib, Kanishka / Rothstein, David M

    Clinics in laboratory medicine

    2018  Volume 39, Issue 1, Page(s) 15–29

    Abstract: B cells shape the alloimmune response through polarized subsets. These cells inhibit or promote immune responses by expressing suppressive or proinflammatory cytokines. Their summed activity dictates the influence of B cells on the alloimmune response. ... ...

    Abstract B cells shape the alloimmune response through polarized subsets. These cells inhibit or promote immune responses by expressing suppressive or proinflammatory cytokines. Their summed activity dictates the influence of B cells on the alloimmune response. We review the evidence for regulatory B cells and effector B cells in mice and humans, discuss current limitations in their phenotypic identification, and discuss regulatory B cells as a signature for clinical renal allograft tolerance and predictive markers for allograft outcomes. We discuss the effects of therapeutic agents on regulatory B cells and potential approaches to augment their numbers as a therapeutic tool.
    MeSH term(s) Animals ; B-Lymphocyte Subsets/metabolism ; B-Lymphocyte Subsets/physiology ; B-Lymphocytes, Regulatory/metabolism ; B-Lymphocytes, Regulatory/physiology ; Biomarkers/metabolism ; Humans ; Mice ; Transplantation Tolerance ; Treatment Outcome ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Biomarkers ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2018-12-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 604580-7
    ISSN 1557-9832 ; 0272-2712
    ISSN (online) 1557-9832
    ISSN 0272-2712
    DOI 10.1016/j.cll.2018.10.011
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    Zs.A 1695: Show issues Location:
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  10. Article ; Online: Transitional B cell cytokines predict renal allograft outcomes.

    Cherukuri, Aravind / Salama, Alan D / Mehta, Rajil / Mohib, Kanishka / Zheng, Leting / Magee, Ciara / Harber, Mark / Stauss, Hans / Baker, Richard J / Tevar, Amit / Landsittel, Douglas / Lakkis, Fadi G / Hariharan, Sundaram / Rothstein, David M

    Science translational medicine

    2021  Volume 13, Issue 582

    Abstract: Early immunological biomarkers that predict rejection and chronic allograft loss are needed to inform preemptive therapy and improve long-term outcomes. Here, we prospectively examined the ratio of interleukin-10 (IL-10) to tumor necrosis factor-α (TNFα) ...

    Abstract Early immunological biomarkers that predict rejection and chronic allograft loss are needed to inform preemptive therapy and improve long-term outcomes. Here, we prospectively examined the ratio of interleukin-10 (IL-10) to tumor necrosis factor-α (TNFα) produced by transitional-1 B cells (T1B) 3 months after transplantation as a predictive biomarker for clinical and subclinical renal allograft rejection and subsequent clinical course. In both Training (
    Language English
    Publishing date 2021-02-24
    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.abe4929
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