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  1. Article ; Online: Electrochemical Cellulase-Linked ELASA for Rapid Liquid Biopsy Testing of Serum HER-2/

    Díaz-Fernández, Ana / Ferapontov, Alexey / Vendelbo, Mikkel Holm / Ferapontova, Elena E

    ACS measurement science au

    2023  Volume 3, Issue 3, Page(s) 226–235

    Abstract: Non-invasive liquid biopsy assays for blood-circulating biomarkers of cancer allow both its early diagnosis and treatment monitoring. Here, we assessed serum levels of protein HER-2/ ...

    Abstract Non-invasive liquid biopsy assays for blood-circulating biomarkers of cancer allow both its early diagnosis and treatment monitoring. Here, we assessed serum levels of protein HER-2/
    Language English
    Publishing date 2023-04-14
    Publishing country United States
    Document type Journal Article
    ISSN 2694-250X
    ISSN (online) 2694-250X
    DOI 10.1021/acsmeasuresciau.2c00067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Haplosufficiency of MHCII in autoreactive germinal center B cells.

    Fahlquist-Hagert, Cecilia / Wittenborn, Thomas R / Ferapontov, Alexey / Jensen, Lisbeth / Terczyńska-Dyla, Ewa / Degn, Søren E

    European journal of immunology

    2023  Volume 54, Issue 1, Page(s) e2350422

    Abstract: Utilizing an autoimmune bone marrow chimera model we determined that B cells depend critically on MHCII expression for participation in the germinal center, but cells displaying a 50% reduction in surface MHCII compete efficiently with their wild-type ... ...

    Abstract Utilizing an autoimmune bone marrow chimera model we determined that B cells depend critically on MHCII expression for participation in the germinal center, but cells displaying a 50% reduction in surface MHCII compete efficiently with their wild-type counterparts. This provides insights into the requirements for germinal center participation.
    MeSH term(s) Germinal Center ; B-Lymphocytes
    Language English
    Publishing date 2023-11-09
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202350422
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Antigen footprint governs activation of the B cell receptor.

    Ferapontov, Alexey / Omer, Marjan / Baudrexel, Isabelle / Nielsen, Jesper Sejrup / Dupont, Daniel Miotto / Juul-Madsen, Kristian / Steen, Philipp / Eklund, Alexandra S / Thiel, Steffen / Vorup-Jensen, Thomas / Jungmann, Ralf / Kjems, Jørgen / Degn, Søren Egedal

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 976

    Abstract: Antigen binding by B cell receptors (BCR) on cognate B cells elicits a response that eventually leads to production of antibodies. However, it is unclear what the distribution of BCRs is on the naïve B cell and how antigen binding triggers the first step ...

    Abstract Antigen binding by B cell receptors (BCR) on cognate B cells elicits a response that eventually leads to production of antibodies. However, it is unclear what the distribution of BCRs is on the naïve B cell and how antigen binding triggers the first step in BCR signaling. Using DNA-PAINT super-resolution microscopy, we find that most BCRs are present as monomers, dimers, or loosely associated clusters on resting B cells, with a nearest-neighbor inter-Fab distance of 20-30 nm. We leverage a Holliday junction nanoscaffold to engineer monodisperse model antigens with precision-controlled affinity and valency, and find that the antigen exerts agonistic effects on the BCR as a function of increasing affinity and avidity. Monovalent macromolecular antigens can activate the BCR at high concentrations, whereas micromolecular antigens cannot, demonstrating that antigen binding does not directly drive activation. Based on this, we propose a BCR activation model determined by the antigen footprint.
    MeSH term(s) Receptors, Antigen, B-Cell/metabolism ; Antigens ; B-Lymphocytes ; Lymphocyte Activation ; Signal Transduction
    Chemical Substances Receptors, Antigen, B-Cell ; Antigens
    Language English
    Publishing date 2023-02-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-36672-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: B cell MHC haplotype affects follicular inclusion, germinal center participation and plasma cell differentiation in a mouse model of lupus.

    Wibrand, Camilla / Wittenborn, Thomas R / Voss, Lasse Frank / Winther, Gudrun / Jensen, Lisbeth / Ferapontov, Alexey / Fonager, Sofie V / Fahlquist-Hagert, Cecilia / Degn, Søren E

    Frontiers in immunology

    2023  Volume 14, Page(s) 1258046

    Abstract: Introduction: MHC class II molecules are essential for appropriate immune responses against pathogens but are also implicated in pathological responses in autoimmune diseases and transplant rejection. Previous studies have shed light on the systemic ... ...

    Abstract Introduction: MHC class II molecules are essential for appropriate immune responses against pathogens but are also implicated in pathological responses in autoimmune diseases and transplant rejection. Previous studies have shed light on the systemic contributions of MHC haplotypes to the development and severity of autoimmune diseases. In this study, we addressed the B cell intrinsic MHC haplotype impact on follicular inclusion, germinal center (GC) participation and plasma cell (PC) differentiation in the context of systemic lupus erythematosus (SLE).
    Methods: We leveraged the 564Igi mouse model which harbors a B cell receptor knock-in from an autoreactive B cell clone recognizing ribonuclear components, including double-stranded DNA (dsDNA). This model recapitulates the central hallmarks of the early stages of SLE. We compared 564Igi heterozygous offspring on either H2b/b, H2b/d, or H2d/d background.
    Results: This revealed significantly higher germinal center (GC) B cell levels in the spleens of H2b/b and H2b/d as compared to H2d/d (p<0.0001) mice. In agreement with this, anti-dsDNA-antibody levels were higher in H2b/b and H2b/d than in H2d/d (p<0.0001), with H2b/b also being higher compared to H2b/d (p<0.01). Specifically, these differences held true both for autoantibodies derived from the knock-in clone and from wild-type (WT) derived clones. In mixed chimeras where 564Igi H2b/b, H2b/d and H2d/d cells competed head-to-head in the same environment, we observed a significantly higher inclusion of H2b/b cells in GC and PC compartments relative to their representation in the B cell repertoire, compared to H2b/d and H2d/d cells. Furthermore, in mixed chimeras in which WT H2b/b and WT H2d/d cells competed for inclusion in GCs associated with an epitope spreading process, H2b/b cells participated to a greater extent and contributed more robustly to the PC compartment. Finally, immature WT H2b/b cells had a higher baseline of BCRs with an autoreactive idiotype and were subject to more stringent negative selection at the transitional stage.
    Discussion: Taken together, our findings demonstrate that B cell intrinsic MHC haplotype governs their capacity for participation in the autoreactive response at multiple levels: follicular inclusion, GC participation, and PC output. These findings pinpoint B cells as central contributors to precipitation of autoimmunity.
    MeSH term(s) Animals ; Mice ; Haplotypes ; Germinal Center ; Lupus Erythematosus, Systemic/genetics ; Autoimmune Diseases ; Cell Differentiation
    Language English
    Publishing date 2023-11-28
    Publishing country Switzerland
    Document type Journal Article ; 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.2023.1258046
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Comparison of gamma and x-ray irradiation for myeloablation and establishment of normal and autoimmune syngeneic bone marrow chimeras.

    Wittenborn, Thomas Rea / Fahlquist Hagert, Cecilia / Ferapontov, Alexey / Fonager, Sofie / Jensen, Lisbeth / Winther, Gudrun / Degn, Søren Egedal

    PloS one

    2021  Volume 16, Issue 3, Page(s) e0247501

    Abstract: Murine bone marrow (BM) chimeras are a versatile and valuable research tool in stem cell and immunology research. Engraftment of donor BM requires myeloablative conditioning of recipients. The most common method used for mice is ionizing radiation, and ... ...

    Abstract Murine bone marrow (BM) chimeras are a versatile and valuable research tool in stem cell and immunology research. Engraftment of donor BM requires myeloablative conditioning of recipients. The most common method used for mice is ionizing radiation, and Cesium-137 gamma irradiators have been preferred. However, radioactive sources are being out-phased worldwide due to safety concerns, and are most commonly replaced by X-ray sources, creating a need to compare these sources regarding efficiency and potential side effects. Prior research has proven both methods capable of efficiently ablating BM cells and splenocytes in mice, but with moderate differences in resultant donor chimerism across tissues. Here, we compared Cesium-137 to 350 keV X-ray irradiation with respect to immune reconstitution, assaying complete, syngeneic BM chimeras and a mixed chimera model of autoimmune disease. Based on dose titration, we find that both gamma and X-ray irradiation can facilitate a near-complete donor chimerism. Mice subjected to 13 Gy Cesium-137 irradiation and reconstituted with syngeneic donor marrow were viable and displayed high donor chimerism, whereas X-ray irradiated mice all succumbed at 13 Gy. However, a similar degree of chimerism as that obtained following 13 Gy gamma irradiation could be achieved by 11 Gy X-ray irradiation, about 85% relative to the gamma dose. In the mixed chimera model of autoimmune disease, we found that a similar autoimmune phenotype could be achieved irrespective of irradiation source used. It is thus possible to compare data generated, regardless of the irradiation source, but every setup and application likely needs individual optimization.
    MeSH term(s) Animals ; Autoimmune Diseases/immunology ; Bone Marrow/radiation effects ; Bone Marrow Cells/radiation effects ; Bone Marrow Transplantation/methods ; Cesium Radioisotopes ; Disease Models, Animal ; Female ; Gamma Rays ; Graft vs Host Disease/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Radiation Chimera/immunology ; Whole-Body Irradiation ; X-Rays
    Chemical Substances Cesium Radioisotopes ; Cesium-137 (4T2E65IAR7)
    Language English
    Publishing date 2021-03-17
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0247501
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Antigen presentation by B cells enables epitope spreading across an MHC barrier.

    Fahlquist-Hagert, Cecilia / Wittenborn, Thomas R / Terczyńska-Dyla, Ewa / Kastberg, Kristian Savstrup / Yang, Emily / Rallistan, Alysa Nicole / Markett, Quinton Raymond / Winther, Gudrun / Fonager, Sofie / Voss, Lasse F / Pedersen, Mathias K / van Campen, Nina / Ferapontov, Alexey / Jensen, Lisbeth / Huang, Jinrong / Nieland, John D / van der Poel, Cees E / Palmfeldt, Johan / Carroll, Michael C /
    Utz, Paul J / Luo, Yonglun / Lin, Lin / Degn, Søren E

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 6941

    Abstract: Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE) ...

    Abstract Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. Here, to test this hypothesis, we used a murine model in which a single B cell clone precipitates an autoreactive response resembling systemic lupus erythematosus (SLE). The initiating clone did not need to enter germinal centers to precipitate epitope spreading. Rather, it localized to extrafollicular splenic bridging channels early in the response. Autoantibody produced by the initiating clone was not sufficient to drive the autoreactive response. Subsequent epitope spreading depended on antigen presentation and was compartmentalized by major histocompatibility complex (MHC). B cells carrying two MHC haplotypes could bridge the MHC barrier between B cells that did not share MHC. Thus, B cells directly relay autoreactivity between two separate compartments of MHC-restricted T cells, leading to inclusion of distinct B cell populations in germinal centers. Our findings demonstrate that B cells initiate and propagate the autoimmune response.
    MeSH term(s) Mice ; Animals ; Antigen Presentation ; Epitopes ; Histocompatibility Antigens Class II/genetics ; B-Lymphocytes ; Lupus Erythematosus, Systemic ; Major Histocompatibility Complex ; Histocompatibility Antigens
    Chemical Substances Epitopes ; Histocompatibility Antigens Class II ; Histocompatibility Antigens
    Language English
    Publishing date 2023-10-31
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-42541-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Study of radiation browning of vegetables in an apparatus with a pseudoliquified (boiling) water

    Ferapontov, A.S

    Konservnaia i ovoshchesushil'naia promyshlennost'. July 1978. (7)

    1978  

    Keywords plant products ; horticultural crops
    Language Russian
    Dates of publication 1978-07
    Size p. 23-26., ill.
    Document type Article
    Note In Russian. ; Title in original language could not be transcribed.
    ISSN 0023-3587
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: Apparatus for radiation frying of vegetables in a quasi-liquid layer

    Ferapontov, A.S

    Konservnaia i ovoshchesushil'naia promyshlennost' Feb 1978. (2)

    1978  

    Keywords plant products ; horticultural crops
    Language Russian
    Dates of publication 1978-02
    Size p. 30-32., ill.
    Document type Article
    Note In Russian. ; Title in original language could not be transcribed.
    ISSN 0023-3587
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Radiation frying of vegetables in a quasi liquid (boiling) layer

    Ferapontov, A.S

    Konservnaia i ovoshchesushil'naia promyshlennost' Sept 1977, 9

    1977  

    Title variant Radiation frying of vegetables in a quasi liquid (boiling) layer [Production of vegetable canned goods]
    Keywords boiling
    Language Russian
    Size p. 11-12.
    Document type Article
    ISSN 0023-3587
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: Line A9-KLM/4 for processing pumpkin and squash

    Ferapontov, A.S / Rotenberg, I.Kh

    Konservnaia i ovoshchesushil'naia promyshlennost'. May 1981. (5)

    1981  

    Title variant Line A9-KLM/4 for processing pumpkin and squash [Production of canned products]
    Keywords horticultural crops ; food processing
    Language Russian
    Dates of publication 1981-05
    Size p. 20-21., ill.
    Document type Article
    Note In Russian. ; Title in original language could not be transcribed.
    ISSN 0023-3587
    Database NAL-Catalogue (AGRICOLA)

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