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

被引：36

作者：

Khairnar, Vishal ^{[1
]}

Duhan, Vikas ^{[1
]}

Maney, Sathish Kumar ^{[2
]}

Honke, Nadine ^{[1
,2
]}

Shaabani, Namir ^{[1
,2
]}

Pandyra, Aleksandra A. ^{[1
]}

Seifert, Marc ^{[3
]}

Pozdeev, Vitaly ^{[2
]}

Xu, Haifeng C. ^{[1
,2
]}

Sharma, Piyush ^{[1
]}

Baldin, Fabian ^{[4
,5
]}

Marquardsen, Florian ^{[4
,5
]}

Merches, Katja ^{[1
,6
]}

Lang, Elisabeth ^{[2
]}

Kirschning, Carsten ^{[7
]}

Westendorf, Astrid M. ^{[7
]}

Hauessinger, Dieter ^{[2
]}

Lang, Florian ^{[6
]}

Dittmer, Ulf ^{[8
]}

Kueppers, Ralf ^{[3
]}

Recher, Mike ^{[4
,5
]}

Hardt, Cornelia ^{[1
]}

Scheffrahn, Inka ^{[9
]}

Beauchemin, Nicole ^{[10
,11
,12
]}

Goethert, Joachim R. ^{[13
]}

Singer, Bernhard B. ^{[14
]}

Lang, Philipp A. ^{[2
,15
]}

Lang, Karl S. ^{[1
,2
]}

机构：

[1] Univ Duisburg Essen, Inst Immunol, Fac Med, D-45147 Essen, Germany

[2] Univ Dusseldorf, Clin Gastroenterol Hepatol & Infect Dis, D-40225 Dusseldorf, Germany

[3] Univ Duisburg Essen, Inst Cell Biol Canc Res, D-45122 Essen, Germany

[4] Univ Basel Hosp, Dept Biomed, Med Outpatient Unit, Clin Primary Immunodeficiency, CH-4031 Basel, Switzerland

[5] Univ Basel Hosp, Dept Biomed, Immunodeficiency Lab, CH-4031 Basel, Switzerland

[6] Univ Tubingen, Dept Physiol 1, D-72076 Tubingen, Germany

[7] Univ Hosp Essen, Inst Med Microbiol, Fac Med, D-45122 Essen, Germany

[8] Univ Duisburg Essen, Inst Virol, D-45147 Essen, Germany

[9] Univ Duisburg Essen, Clin Gastroenterol & Hepatol, D-45147 Essen, Germany

[10] Rosalind & Morris Goodman Canc Ctr, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

[11] Rosalind & Morris Goodman Canc Ctr, Dept Med, Montreal, PQ H3G 1Y6, Canada

[12] Rosalind & Morris Goodman Canc Ctr, Dept Oncol, Montreal, PQ H3G 1Y6, Canada

[13] Univ Hosp Essen, Dept Hematol, West German Ctr WTZ, D-45147 Essen, Germany

[14] Univ Duisburg Essen, Inst Anat, Fac Med, D-45147 Essen, Germany

[15] Univ Dusseldorf, Dept Mol Med 2, D-40225 Dusseldorf, Germany

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

加拿大健康研究院; 瑞士国家科学基金会;

关键词：

ALDRICH-SYNDROME PROTEIN; SUBCAPSULAR SINUS MACROPHAGES; BRUTON TYROSINE KINASE; BILIARY GLYCOPROTEIN; ADHESION MOLECULE; T-CELLS; LYMPHOCYTE DEVELOPMENT; CYTOPLASMIC DOMAIN; ADAPTIVE IMMUNITY; EPITHELIAL-CELLS;

D O I：

10.1038/ncomms7217

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-kappa B-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.

引用

页数：13

共 60 条

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