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

VL - 171

SP - 1722

EP - 1731

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -