CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

Vishal Khairnar, Vikas Duhan, Sathish Kumar Maney, Nadine Honke, Namir Shaabani, Aleksandra A. Pandyra, Marc Seifert, Vitaly Pozdeev, Haifeng C. Xu, Piyush Sharma, Fabian Baldin, Florian Marquardsen, Katja Merches, Elisabeth Lang, Carsten Kirschning, Astrid M. Westendorf, Dieter Häussinger, Florian Lang, Ulf Dittmer, Ralf Küppers, Mike Recher, Cornelia Hardt, Inka Scheffrahn, Nicole Beauchemin, Joachim R. Göthert, Bernhard B. Singer, Philipp A. Lang and Karl S. Lang ()
Additional contact information
Vishal Khairnar: Institute of Immunology, Medical Faculty, University of Duisburg-Essen
Vikas Duhan: Institute of Immunology, Medical Faculty, University of Duisburg-Essen
Sathish Kumar Maney: Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University
Nadine Honke: Institute of Immunology, Medical Faculty, University of Duisburg-Essen
Namir Shaabani: Institute of Immunology, Medical Faculty, University of Duisburg-Essen
Aleksandra A. Pandyra: Institute of Immunology, Medical Faculty, University of Duisburg-Essen
Marc Seifert: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen
Vitaly Pozdeev: Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University
Haifeng C. Xu: Institute of Immunology, Medical Faculty, University of Duisburg-Essen
Piyush Sharma: Institute of Immunology, Medical Faculty, University of Duisburg-Essen
Fabian Baldin: Clinic for Primary Immunodeficiency, Medical Outpatient Unit and Immunodeficiency Laboratory, University Hospital
Florian Marquardsen: Clinic for Primary Immunodeficiency, Medical Outpatient Unit and Immunodeficiency Laboratory, University Hospital
Katja Merches: Institute of Immunology, Medical Faculty, University of Duisburg-Essen
Elisabeth Lang: Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University
Carsten Kirschning: Institute of Medical Microbiology, Faculty of Medicine, University Hospital Essen
Astrid M. Westendorf: Institute of Medical Microbiology, Faculty of Medicine, University Hospital Essen
Dieter Häussinger: Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University
Florian Lang: University of Tuebingen
Ulf Dittmer: Institute of Virology, University of Duisburg-Essen
Ralf Küppers: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen
Mike Recher: Clinic for Primary Immunodeficiency, Medical Outpatient Unit and Immunodeficiency Laboratory, University Hospital
Cornelia Hardt: Institute of Immunology, Medical Faculty, University of Duisburg-Essen
Inka Scheffrahn: Clinic of Gastroenterology and Hepatology, University of Duisburg-Essen
Nicole Beauchemin: Rosalind and Morris Goodman Cancer Centre, Medicine and Oncology, McIntyre Medical Science Building
Joachim R. Göthert: West German Cancer Center (WTZ), University Hospital Essen
Bernhard B. Singer: Institute of Anatomy, Medical Faculty, University of Duisburg-Essen
Philipp A. Lang: Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University
Karl S. Lang: Institute of Immunology, Medical Faculty, University of Duisburg-Essen

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1−/− mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1−/− mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses.

Date: 2015
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DOI: 10.1038/ncomms7217

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