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

[1] Peripheral B cell subsets
Allman, David
Pillai, Shiv
[J]. CURRENT OPINION IN IMMUNOLOGY, 2008, 20 (02) : 149 - 157
[2] BRUTON TYROSINE KINASE IS TYROSINE-PHOSPHORYLATED AND ACTIVATED IN PRE-B LYMPHOCYTES AND RECEPTOR-LIGATED B-CELLS
AOKI, Y
ISSELBACHER, KJ
PILLAI, S
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (22) : 10606 - 10609
[3] Host-related carcinoembryonic antigen cell adhesion molecule 1 promotes metastasis of colorectal cancer
Arabzadeh, A.
Chan, C.
Nouvion, A-L
Breton, V.
Benlolo, S.
DeMarte, L.
Turbide, C.
Brodt, P.
Ferri, L.
Beauchemin, N.
[J]. ONCOGENE, 2013, 32 (07) : 849 - 860
[4] Involvement of Wiskott-Aldrich syndrome protein in B-Cell cytoplasmic tyrosine kinase pathway
Baba, Y
Nonoyama, S
Matsushita, M
Yamadori, T
Hashimoto, S
Imai, K
Arai, S
Kunikata, T
Kurimoto, M
Kurosaki, T
Ochs, HD
Yata, J
Kishimoto, T
Tsukada, S
[J]. BLOOD, 1999, 93 (06) : 2003 - 2012
[5] QUANTIFICATION OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS WITH AN IMMUNOLOGICAL FOCUS ASSAY IN 24-WELL OR 96-WELL PLATES
BATTEGAY, M
COOPER, S
ALTHAGE, A
BANZIGER, J
HENGARTNER, H
ZINKERNAGEL, RM
[J]. JOURNAL OF VIROLOGICAL METHODS, 1991, 33 (1-2) : 191 - 198
[6] Association of biliary glycoprotein with protein tyrosine phosphatase SHP-1 in malignant colon epithelial cells
Beauchemin, N
Kunath, T
Robitaille, J
Chow, B
Turbide, C
Daniels, E
Veillette, A
[J]. ONCOGENE, 1997, 14 (07) : 783 - 790
[7] Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis
Beauchemin, Nicole
Arabzadeh, Azadeh
[J]. CANCER AND METASTASIS REVIEWS, 2013, 32 (3-4) : 643 - 671
[8] Immunity to viruses in B cell-deficient mice: Influence of antibodies on virus persistence and on T cell memory
Brundler, MA
Aichele, P
Bachmann, M
Kitamura, D
Rajewsky, K
Zinkernagel, RM
[J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (09) : 2257 - 2262
[9] The cell-cell adhesion molecule carcinoembryonic antigen-related cellular adhesion molecule 1 inhibits IL-2 production and proliferation in human T cells by association. with Src homology protein-1 and down-regulates IL-2 receptor
Chen, CJ
Shively, JE
[J]. JOURNAL OF IMMUNOLOGY, 2004, 172 (06) : 3544 - 3552
[10] The Short Isoform of the CEACAM1 Receptor in Intestinal T Cells Regulates Mucosal Immunity and Homeostasis via Tfh Cell Induction
Chen, Lanfen
Chen, Zhangguo
Baker, Kristi
Halvorsen, Elizabeth M.
da Cunha, Andre Pires
Flak, Magdalena B.
Gerber, Georg
Huang, Yu-Hwa
Hosomi, Shuhei
Arthur, Janelle C.
Dery, Ken J.
Nagaishi, Takashi
Beauchemin, Nicole
Holmes, Kathryn V.
Ho, Joshua W. K.
Shively, John E.
Jobin, Christian
Onderdonk, Andrew B.
Bry, Lynn
Weiner, Howard L.
Higgins, Darren E.
Blumberg, Richard S.
[J]. IMMUNITY, 2012, 37 (05) : 930 - 946

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