CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells

Tan Jinquan; Henrik H Jacobi; Chen Jing; Anders Millner; Eva Sten; Lars Hviid; Liu Anting; Lars P Ryder; Christian Glue; Per S Skov; Elizabeth Jarman; Kasper Lamberth; Hans-Jørgen Malling; Lars K Poulsen

CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells

Tan Jinquan, Henrik H Jacobi, Chen Jing, Anders Millner, Eva Sten, Lars Hviid, Liu Anting, Lars P Ryder, Christian Glue, Per S Skov, Elizabeth Jarman, Kasper Lamberth, Hans-Jørgen Malling, Lars K Poulsen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

30 Citationer (Scopus)

Abstract

Udgivelsesdato: 2003-Aug-15

Originalsprog	Engelsk
Tidsskrift	Journal of Immunology
Vol/bind	171
Udgave nummer	4
Sider (fra-til)	1722-31
Antal sider	9
ISSN	0022-1767
Status	Udgivet - 2003

Bibliografisk note

Keywords: Antigens, CD95; Apoptosis; B-Lymphocyte Subsets; Cell Adhesion; Cell Line; Cells, Cultured; Chemokine CCL11; Chemokines, CC; Chemotaxis, Leukocyte; Child; Fas Ligand Protein; Humans; Interleukin-2; Interleukin-4; Ligands; Membrane Glycoproteins; Receptors, CCR3; Receptors, Chemokine; Receptors, Tumor Necrosis Factor; Tonsil; Tumor Cells, Cultured

Citationsformater

@article{fe9d92107dcd11dd81b0000ea68e967b,

title = "CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells",

abstract = "We report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (approximately 98% CCR3(+)). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19(+) (approximately 40% apoptotic cells) B cell cultures as well as B cell lines, but has no effect on chemotaxis or cell adhesion. Freshly isolated B cells express low levels of CD95 and CD95 ligand (CD95L) (19 and 21%, respectively). Expression is up-regulated on culture in the presence of a combination of IL-2, IL-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant death signaling pathways, which include an increase in levels of Bcl-2 expression, its functional activity, and the release of cytochrome c from the mitochondria into the cytosol. These events initiate a cascade of enzymatic processes of the caspase family, culminating in programmed cell death. Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests a therapeutic modality in the treatment of B cell lymphoma.",

author = "Tan Jinquan and Jacobi, {Henrik H} and Chen Jing and Anders Millner and Eva Sten and Lars Hviid and Liu Anting and Ryder, {Lars P} and Christian Glue and Skov, {Per S} and Elizabeth Jarman and Kasper Lamberth and Hans-J{\o}rgen Malling and Poulsen, {Lars K}",

note = "Keywords: Antigens, CD95; Apoptosis; B-Lymphocyte Subsets; Cell Adhesion; Cell Line; Cells, Cultured; Chemokine CCL11; Chemokines, CC; Chemotaxis, Leukocyte; Child; Fas Ligand Protein; Humans; Interleukin-2; Interleukin-4; Ligands; Membrane Glycoproteins; Receptors, CCR3; Receptors, Chemokine; Receptors, Tumor Necrosis Factor; Tonsil; Tumor Cells, Cultured",

year = "2003",

language = "English",

volume = "171",

pages = "1722--31",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "4",

}

TY - JOUR

T1 - CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells

AU - Jinquan, Tan

AU - Jacobi, Henrik H

AU - Jing, Chen

AU - Millner, Anders

AU - Sten, Eva

AU - Hviid, Lars

AU - Anting, Liu

AU - Ryder, Lars P

AU - Glue, Christian

AU - Skov, Per S

AU - Jarman, Elizabeth

AU - Lamberth, Kasper

AU - Malling, Hans-Jørgen

AU - Poulsen, Lars K

N1 - Keywords: Antigens, CD95; Apoptosis; B-Lymphocyte Subsets; Cell Adhesion; Cell Line; Cells, Cultured; Chemokine CCL11; Chemokines, CC; Chemotaxis, Leukocyte; Child; Fas Ligand Protein; Humans; Interleukin-2; Interleukin-4; Ligands; Membrane Glycoproteins; Receptors, CCR3; Receptors, Chemokine; Receptors, Tumor Necrosis Factor; Tonsil; Tumor Cells, Cultured

PY - 2003

Y1 - 2003

N2 - We report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (approximately 98% CCR3(+)). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19(+) (approximately 40% apoptotic cells) B cell cultures as well as B cell lines, but has no effect on chemotaxis or cell adhesion. Freshly isolated B cells express low levels of CD95 and CD95 ligand (CD95L) (19 and 21%, respectively). Expression is up-regulated on culture in the presence of a combination of IL-2, IL-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant death signaling pathways, which include an increase in levels of Bcl-2 expression, its functional activity, and the release of cytochrome c from the mitochondria into the cytosol. These events initiate a cascade of enzymatic processes of the caspase family, culminating in programmed cell death. Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests a therapeutic modality in the treatment of B cell lymphoma.

AB - We report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (approximately 98% CCR3(+)). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19(+) (approximately 40% apoptotic cells) B cell cultures as well as B cell lines, but has no effect on chemotaxis or cell adhesion. Freshly isolated B cells express low levels of CD95 and CD95 ligand (CD95L) (19 and 21%, respectively). Expression is up-regulated on culture in the presence of a combination of IL-2, IL-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant death signaling pathways, which include an increase in levels of Bcl-2 expression, its functional activity, and the release of cytochrome c from the mitochondria into the cytosol. These events initiate a cascade of enzymatic processes of the caspase family, culminating in programmed cell death. Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests a therapeutic modality in the treatment of B cell lymphoma.

M3 - Journal article

C2 - 12902471

SN - 0022-1767

VL - 171

SP - 1722

EP - 1731

JO - Journal of Immunology

JF - Journal of Immunology

IS - 4

ER -