Khairnar Vishal, Duhan Vikas, Maney Sathish Kumar, Honke Nadine, Shaabani Namir, Pandyra Aleksandra A, Seifert Marc, Pozdeev Vitaly, Xu Haifeng C, Sharma Piyush, Baldin Fabian, Marquardsen Florian, Merches Katja, Lang Elisabeth, Kirschning Carsten, Westendorf Astrid M, Häussinger Dieter, Lang Florian, Dittmer Ulf, Küppers Ralf, Recher Mike, Hardt Cornelia, Scheffrahn Inka, Beauchemin Nicole, Göthert Joachim R, Singer Bernhard B, Lang Philipp A, Lang Karl S
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf 40225, Germany.
Nat Commun. 2015 Feb 18;6:6217. doi: 10.1038/ncomms7217.
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.
B细胞对于抗病毒免疫防御至关重要，因为它们能产生中和抗体、呈递抗原并维持淋巴结构。我们在此表明，CEACAM1的内在信号传导对于产生有效的B细胞反应至关重要。尽管CEACAM1对B细胞增殖的影响有限，但CEACAM1的表达通过BTK/Syk/NF-κB轴诱导增殖B细胞的存活。在幼稚的Ceacam1(-/-)小鼠中，这种信号级联的缺失限制了B细胞的存活。在用细胞病变性水疱性口炎病毒进行全身感染期间，Ceacam1(-/-)小鼠几乎无法诱导中和抗体反应，并在感染后早期死亡。因此，我们发现CEACAM1是B细胞存活的关键调节因子，影响B细胞数量和保护性抗病毒抗体反应。
