EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies

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EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies. / Niss Arfelt, Kristine; Barington, Line; Benned-Jensen, Tau; Kubale, Valentina; Kovalchuk, Alexander L; Daugvilaite, Viktorija; Pravsgaard Christensen, Jan; Randrup Thomsen, Allan; Egerod, Kristoffer L; Bassi, Maria R; Spiess, Katja; Schwartz, Thue W; Wang, Hongsheng; Morse, Herbert C; Holst, Peter J; Rosenkilde, Mette M.

In: Blood, Vol. 129, No. 7, 2017, p. 866-878.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Niss Arfelt, K, Barington, L, Benned-Jensen, T, Kubale, V, Kovalchuk, AL, Daugvilaite, V, Pravsgaard Christensen, J, Randrup Thomsen, A, Egerod, KL, Bassi, MR, Spiess, K, Schwartz, TW, Wang, H, Morse, HC, Holst, PJ & Rosenkilde, MM 2017, 'EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies', Blood, vol. 129, no. 7, pp. 866-878. https://doi.org/10.1182/blood-2016-02-697185

APA

Niss Arfelt, K., Barington, L., Benned-Jensen, T., Kubale, V., Kovalchuk, A. L., Daugvilaite, V., Pravsgaard Christensen, J., Randrup Thomsen, A., Egerod, K. L., Bassi, M. R., Spiess, K., Schwartz, T. W., Wang, H., Morse, H. C., Holst, P. J., & Rosenkilde, M. M. (2017). EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies. Blood, 129(7), 866-878. https://doi.org/10.1182/blood-2016-02-697185

Vancouver

Niss Arfelt K, Barington L, Benned-Jensen T, Kubale V, Kovalchuk AL, Daugvilaite V et al. EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies. Blood. 2017;129(7):866-878. https://doi.org/10.1182/blood-2016-02-697185

Author

Niss Arfelt, Kristine ; Barington, Line ; Benned-Jensen, Tau ; Kubale, Valentina ; Kovalchuk, Alexander L ; Daugvilaite, Viktorija ; Pravsgaard Christensen, Jan ; Randrup Thomsen, Allan ; Egerod, Kristoffer L ; Bassi, Maria R ; Spiess, Katja ; Schwartz, Thue W ; Wang, Hongsheng ; Morse, Herbert C ; Holst, Peter J ; Rosenkilde, Mette M. / EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies. In: Blood. 2017 ; Vol. 129, No. 7. pp. 866-878.

Bibtex

@article{8ec7dc4a8015476f922f03d8f04fe7ea,
title = "EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies",
abstract = "Human and mouse chronic lymphocytic leukemia (CLL) develop from CD5+ B cells that in mice and macaques are known to define the distinct B1a B cell lineage. B1a cells are characterized by lack of germinal center development and the B1a cell population is increased in mice with reduced germinal center formation. As a major mediator of follicular B cell migration, the G protein-coupled receptor (GPCR) Epstein Barr virus-induced gene 2 (EBI2 or GPR183) directs B cell migration in the lymphoid follicles in response to its endogenous ligands, oxysterols. Thus, upregulation of EBI2 drives the B cells towards the extrafollicular area, whereas downregulation is essential for germinal center formation. We therefore speculated whether increased expression of EBI2 would lead to an expanded B1 cell subset and, ultimately, progression to chronic lymphocytic leukemia. Here we demonstrate that B cell-targeted expression of human EBI2 in mice reduces germinal center-dependent immune responses, reduces total IgM and IgG levels, and leads to increased proliferation and upregulation of cellular oncogenes. Furthermore, hEBI2 overexpression leads to an abnormally expanded CD5+ B1a B cell subset present as early as 4 days after birth, late-onset lymphoid cancer development and premature death. These findings are highly similar to those observed in CLL patients and identify EBI2 as a promoter of B cell malignancies.",
author = "{Niss Arfelt}, Kristine and Line Barington and Tau Benned-Jensen and Valentina Kubale and Kovalchuk, {Alexander L} and Viktorija Daugvilaite and {Pravsgaard Christensen}, Jan and {Randrup Thomsen}, Allan and Egerod, {Kristoffer L} and Bassi, {Maria R} and Katja Spiess and Schwartz, {Thue W} and Hongsheng Wang and Morse, {Herbert C} and Holst, {Peter J} and Rosenkilde, {Mette M}",
note = "Copyright {\textcopyright} 2016 American Society of Hematology.",
year = "2017",
doi = "10.1182/blood-2016-02-697185",
language = "English",
volume = "129",
pages = "866--878",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "7",

}

RIS

TY - JOUR

T1 - EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies

AU - Niss Arfelt, Kristine

AU - Barington, Line

AU - Benned-Jensen, Tau

AU - Kubale, Valentina

AU - Kovalchuk, Alexander L

AU - Daugvilaite, Viktorija

AU - Pravsgaard Christensen, Jan

AU - Randrup Thomsen, Allan

AU - Egerod, Kristoffer L

AU - Bassi, Maria R

AU - Spiess, Katja

AU - Schwartz, Thue W

AU - Wang, Hongsheng

AU - Morse, Herbert C

AU - Holst, Peter J

AU - Rosenkilde, Mette M

N1 - Copyright © 2016 American Society of Hematology.

PY - 2017

Y1 - 2017

N2 - Human and mouse chronic lymphocytic leukemia (CLL) develop from CD5+ B cells that in mice and macaques are known to define the distinct B1a B cell lineage. B1a cells are characterized by lack of germinal center development and the B1a cell population is increased in mice with reduced germinal center formation. As a major mediator of follicular B cell migration, the G protein-coupled receptor (GPCR) Epstein Barr virus-induced gene 2 (EBI2 or GPR183) directs B cell migration in the lymphoid follicles in response to its endogenous ligands, oxysterols. Thus, upregulation of EBI2 drives the B cells towards the extrafollicular area, whereas downregulation is essential for germinal center formation. We therefore speculated whether increased expression of EBI2 would lead to an expanded B1 cell subset and, ultimately, progression to chronic lymphocytic leukemia. Here we demonstrate that B cell-targeted expression of human EBI2 in mice reduces germinal center-dependent immune responses, reduces total IgM and IgG levels, and leads to increased proliferation and upregulation of cellular oncogenes. Furthermore, hEBI2 overexpression leads to an abnormally expanded CD5+ B1a B cell subset present as early as 4 days after birth, late-onset lymphoid cancer development and premature death. These findings are highly similar to those observed in CLL patients and identify EBI2 as a promoter of B cell malignancies.

AB - Human and mouse chronic lymphocytic leukemia (CLL) develop from CD5+ B cells that in mice and macaques are known to define the distinct B1a B cell lineage. B1a cells are characterized by lack of germinal center development and the B1a cell population is increased in mice with reduced germinal center formation. As a major mediator of follicular B cell migration, the G protein-coupled receptor (GPCR) Epstein Barr virus-induced gene 2 (EBI2 or GPR183) directs B cell migration in the lymphoid follicles in response to its endogenous ligands, oxysterols. Thus, upregulation of EBI2 drives the B cells towards the extrafollicular area, whereas downregulation is essential for germinal center formation. We therefore speculated whether increased expression of EBI2 would lead to an expanded B1 cell subset and, ultimately, progression to chronic lymphocytic leukemia. Here we demonstrate that B cell-targeted expression of human EBI2 in mice reduces germinal center-dependent immune responses, reduces total IgM and IgG levels, and leads to increased proliferation and upregulation of cellular oncogenes. Furthermore, hEBI2 overexpression leads to an abnormally expanded CD5+ B1a B cell subset present as early as 4 days after birth, late-onset lymphoid cancer development and premature death. These findings are highly similar to those observed in CLL patients and identify EBI2 as a promoter of B cell malignancies.

U2 - 10.1182/blood-2016-02-697185

DO - 10.1182/blood-2016-02-697185

M3 - Journal article

C2 - 28003273

VL - 129

SP - 866

EP - 878

JO - Blood

JF - Blood

SN - 0006-4971

IS - 7

ER -

ID: 171549286