T cell leukemia/lymphoma 1 and galectin-1 regulate survival/cell death pathways in human naive and IgM+ memory B cells through altering balances in Bcl-2 family proteins

Siamak Jabbarzadeh Tabrizi, Hiroaki Niiro, Mariko Masui, Goichi Yoshimoto, Tadafumi Iino, Yoshikane Kikushige, Takahiro Wakasaki, Eishi Baba, Shinji Shimoda, Toshihiro Miyamoto, Toshiro Hara, Koichi Akashi

研究成果: ジャーナルへの寄稿記事

35 引用 (Scopus)

抄録

BCR signaling plays a critical role in purging the self-reactive repertoire, or in rendering it anergic to establish self-tolerance in the periphery. Differences in self-reactivity between human naive and IgM + memory B cells may reflect distinct mechanisms by which BCR signaling dictates their survival and death. Here we demonstrate that BCR stimulation protected naive B cells from apoptosis with induction of prosurvival Bcl-2 family proteins, Bcl-xL and Mcl-1, whereas it rather accelerated apoptosis of IgM+ memory B cells by inducing proapoptotic BH3-only protein Bim. We found that BCR-mediated PI3K activation induced the expression of Mcl-1, whereas it inhibited Bim expression in B cells. Phosphorylation of Akt, a downstream molecule of PI3K, was more sustained in naive than IgM+ memory B cells. Abundant expression of T cell leukemia/lymphoma 1 (Tcl1), an Akt coactivator, was found in naive B cells, and enforced expression of Tcl1 induced a high level of Mcl-1 expression, resulting in prolonged B cell survival. In contrast, Galectin-1 (Gal-1) was abundantly expressed in IgM+ memory B cells, and inhibited Akt phosphorylation, leading to Bim up-regulation. Enforced expression of Gal-1 induced accelerated apoptosis in B cells. These results suggest that a unique set of molecules, Tcl1 and Gal-1, defines distinct BCR signaling cascades, dictating survival and death of human naive and IgM+ memory B cells.

元の言語英語
ページ(範囲)1490-1499
ページ数10
ジャーナルJournal of Immunology
182
発行部数3
DOI
出版物ステータス出版済み - 2 1 2009

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Galectin 1
T-Cell Leukemia
T-Cell Lymphoma
Immunoglobulin M
B-Lymphocytes
Cell Death
Survival
Proteins
Apoptosis
Phosphatidylinositol 3-Kinases
Phosphorylation
Self Tolerance
Cell Survival
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Immunology

これを引用

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title = "T cell leukemia/lymphoma 1 and galectin-1 regulate survival/cell death pathways in human naive and IgM+ memory B cells through altering balances in Bcl-2 family proteins",
abstract = "BCR signaling plays a critical role in purging the self-reactive repertoire, or in rendering it anergic to establish self-tolerance in the periphery. Differences in self-reactivity between human naive and IgM + memory B cells may reflect distinct mechanisms by which BCR signaling dictates their survival and death. Here we demonstrate that BCR stimulation protected naive B cells from apoptosis with induction of prosurvival Bcl-2 family proteins, Bcl-xL and Mcl-1, whereas it rather accelerated apoptosis of IgM+ memory B cells by inducing proapoptotic BH3-only protein Bim. We found that BCR-mediated PI3K activation induced the expression of Mcl-1, whereas it inhibited Bim expression in B cells. Phosphorylation of Akt, a downstream molecule of PI3K, was more sustained in naive than IgM+ memory B cells. Abundant expression of T cell leukemia/lymphoma 1 (Tcl1), an Akt coactivator, was found in naive B cells, and enforced expression of Tcl1 induced a high level of Mcl-1 expression, resulting in prolonged B cell survival. In contrast, Galectin-1 (Gal-1) was abundantly expressed in IgM+ memory B cells, and inhibited Akt phosphorylation, leading to Bim up-regulation. Enforced expression of Gal-1 induced accelerated apoptosis in B cells. These results suggest that a unique set of molecules, Tcl1 and Gal-1, defines distinct BCR signaling cascades, dictating survival and death of human naive and IgM+ memory B cells.",
author = "Tabrizi, {Siamak Jabbarzadeh} and Hiroaki Niiro and Mariko Masui and Goichi Yoshimoto and Tadafumi Iino and Yoshikane Kikushige and Takahiro Wakasaki and Eishi Baba and Shinji Shimoda and Toshihiro Miyamoto and Toshiro Hara and Koichi Akashi",
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T1 - T cell leukemia/lymphoma 1 and galectin-1 regulate survival/cell death pathways in human naive and IgM+ memory B cells through altering balances in Bcl-2 family proteins

AU - Tabrizi, Siamak Jabbarzadeh

AU - Niiro, Hiroaki

AU - Masui, Mariko

AU - Yoshimoto, Goichi

AU - Iino, Tadafumi

AU - Kikushige, Yoshikane

AU - Wakasaki, Takahiro

AU - Baba, Eishi

AU - Shimoda, Shinji

AU - Miyamoto, Toshihiro

AU - Hara, Toshiro

AU - Akashi, Koichi

PY - 2009/2/1

Y1 - 2009/2/1

N2 - BCR signaling plays a critical role in purging the self-reactive repertoire, or in rendering it anergic to establish self-tolerance in the periphery. Differences in self-reactivity between human naive and IgM + memory B cells may reflect distinct mechanisms by which BCR signaling dictates their survival and death. Here we demonstrate that BCR stimulation protected naive B cells from apoptosis with induction of prosurvival Bcl-2 family proteins, Bcl-xL and Mcl-1, whereas it rather accelerated apoptosis of IgM+ memory B cells by inducing proapoptotic BH3-only protein Bim. We found that BCR-mediated PI3K activation induced the expression of Mcl-1, whereas it inhibited Bim expression in B cells. Phosphorylation of Akt, a downstream molecule of PI3K, was more sustained in naive than IgM+ memory B cells. Abundant expression of T cell leukemia/lymphoma 1 (Tcl1), an Akt coactivator, was found in naive B cells, and enforced expression of Tcl1 induced a high level of Mcl-1 expression, resulting in prolonged B cell survival. In contrast, Galectin-1 (Gal-1) was abundantly expressed in IgM+ memory B cells, and inhibited Akt phosphorylation, leading to Bim up-regulation. Enforced expression of Gal-1 induced accelerated apoptosis in B cells. These results suggest that a unique set of molecules, Tcl1 and Gal-1, defines distinct BCR signaling cascades, dictating survival and death of human naive and IgM+ memory B cells.

AB - BCR signaling plays a critical role in purging the self-reactive repertoire, or in rendering it anergic to establish self-tolerance in the periphery. Differences in self-reactivity between human naive and IgM + memory B cells may reflect distinct mechanisms by which BCR signaling dictates their survival and death. Here we demonstrate that BCR stimulation protected naive B cells from apoptosis with induction of prosurvival Bcl-2 family proteins, Bcl-xL and Mcl-1, whereas it rather accelerated apoptosis of IgM+ memory B cells by inducing proapoptotic BH3-only protein Bim. We found that BCR-mediated PI3K activation induced the expression of Mcl-1, whereas it inhibited Bim expression in B cells. Phosphorylation of Akt, a downstream molecule of PI3K, was more sustained in naive than IgM+ memory B cells. Abundant expression of T cell leukemia/lymphoma 1 (Tcl1), an Akt coactivator, was found in naive B cells, and enforced expression of Tcl1 induced a high level of Mcl-1 expression, resulting in prolonged B cell survival. In contrast, Galectin-1 (Gal-1) was abundantly expressed in IgM+ memory B cells, and inhibited Akt phosphorylation, leading to Bim up-regulation. Enforced expression of Gal-1 induced accelerated apoptosis in B cells. These results suggest that a unique set of molecules, Tcl1 and Gal-1, defines distinct BCR signaling cascades, dictating survival and death of human naive and IgM+ memory B cells.

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JO - Journal of Immunology

JF - Journal of Immunology

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