Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus
Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/96518 https://orcid.org/0000-0002-1090-6071 |
| _version_ | 1826207083860590592 |
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| author | Dougan, Stephanie K. Ashour, Joseph Karssemeijer, Roos A. Popp, Maximilian W. Avalos, Ana M. Barisa, Marta Altenburg, Arwen F. Ingram, Jessica R. Cragnolini, Juan J. Guo, Chunguang Alt, Frederick W. Jaenisch, Rudolf Ploegh, Hidde |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Dougan, Stephanie K. Ashour, Joseph Karssemeijer, Roos A. Popp, Maximilian W. Avalos, Ana M. Barisa, Marta Altenburg, Arwen F. Ingram, Jessica R. Cragnolini, Juan J. Guo, Chunguang Alt, Frederick W. Jaenisch, Rudolf Ploegh, Hidde |
| author_sort | Dougan, Stephanie K. |
| collection | MIT |
| description | Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response. |
| first_indexed | 2024-09-23T13:43:38Z |
| format | Article |
| id | mit-1721.1/96518 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:43:38Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/965182022-09-28T15:46:40Z Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus Dougan, Stephanie K. Ashour, Joseph Karssemeijer, Roos A. Popp, Maximilian W. Avalos, Ana M. Barisa, Marta Altenburg, Arwen F. Ingram, Jessica R. Cragnolini, Juan J. Guo, Chunguang Alt, Frederick W. Jaenisch, Rudolf Ploegh, Hidde Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Jaenisch, Rudolf Ploegh, Hidde Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response. National Institutes of Health (U.S.) 2015-04-10T17:05:08Z 2015-04-10T17:05:08Z 2013-10 2013-05 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/96518 Dougan, Stephanie K., Joseph Ashour, Roos A. Karssemeijer, Maximilian W. Popp, Ana M. Avalos, Marta Barisa, Arwen F. Altenburg, et al. “Antigen-Specific B-Cell Receptor Sensitizes B Cells to Infection by Influenza Virus.” Nature 503, no. 7476 (October 20, 2013): 406–409. https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1038/nature12637 Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Dougan, Stephanie K. Ashour, Joseph Karssemeijer, Roos A. Popp, Maximilian W. Avalos, Ana M. Barisa, Marta Altenburg, Arwen F. Ingram, Jessica R. Cragnolini, Juan J. Guo, Chunguang Alt, Frederick W. Jaenisch, Rudolf Ploegh, Hidde Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus |
| title | Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus |
| title_full | Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus |
| title_fullStr | Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus |
| title_full_unstemmed | Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus |
| title_short | Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus |
| title_sort | antigen specific b cell receptor sensitizes b cells to infection by influenza virus |
| url | http://hdl.handle.net/1721.1/96518 https://orcid.org/0000-0002-1090-6071 |
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