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Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL
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| Zeitschriftentitel: | The Journal of Immunology |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | The Journal of Immunology, 172, 2004, 5, S. 3268-3279 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The American Association of Immunologists
|
| Schlagwörter: |
| author_facet |
He, Bing Chadburn, Amy Jou, Erin Schattner, Elaine J. Knowles, Daniel M. Cerutti, Andrea He, Bing Chadburn, Amy Jou, Erin Schattner, Elaine J. Knowles, Daniel M. Cerutti, Andrea |
|---|---|
| author |
He, Bing Chadburn, Amy Jou, Erin Schattner, Elaine J. Knowles, Daniel M. Cerutti, Andrea |
| spellingShingle |
He, Bing Chadburn, Amy Jou, Erin Schattner, Elaine J. Knowles, Daniel M. Cerutti, Andrea The Journal of Immunology Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL Immunology Immunology and Allergy |
| author_sort |
he, bing |
| spelling |
He, Bing Chadburn, Amy Jou, Erin Schattner, Elaine J. Knowles, Daniel M. Cerutti, Andrea 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.172.5.3268 <jats:title>Abstract</jats:title> <jats:p>The mechanisms underlying the autonomous accumulation of malignant B cells remain elusive. We show in this study that non-Hodgkin’s lymphoma (NHL) B cells express B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), two powerful B cell-activating molecules usually expressed by myeloid cells. In addition, NHL B cells express BAFF receptor, which binds BAFF, as well as transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation Ag (BCMA), which bind both BAFF and APRIL. Neutralization of endogenous BAFF and APRIL by soluble TACI and BCMA decoy receptors attenuates the survival of NHL B cells, decreases activation of the prosurvival transcription factor NF-κB, down-regulates the antiapoptotic proteins Bcl-2 and Bcl-xL, and up-regulates the proapoptotic protein Bax. Conversely, exposure of NHL B cells to recombinant or myeloid cell-derived BAFF and APRIL attenuates apoptosis, increases NF-κB activation, up-regulates Bcl-2 and Bcl-xL, and down-regulates Bax. In some NHLs, exogenous BAFF and APRIL up-regulate c-Myc, an inducer of cell proliferation; down-regulate p53, an inhibitor of cell proliferation; and increase Bcl-6, an inhibitor of B cell differentiation. By showing that nonmalignant B cells up-regulate BAFF and APRIL upon stimulation by T cell CD40 ligand, our findings indicate that NHL B cells deregulate an otherwise physiological autocrine survival pathway to evade apoptosis. Thus, neutralization of BAFF and APRIL by soluble TACI and BCMA decoy receptors could be useful to dampen the accumulation of malignant B cells in NHL patients.</jats:p> Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL The Journal of Immunology |
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The American Association of Immunologists, 2004 |
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The American Association of Immunologists, 2004 |
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0022-1767 1550-6606 |
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| title |
Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_unstemmed |
Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_full |
Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_fullStr |
Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_full_unstemmed |
Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_short |
Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_sort |
lymphoma b cells evade apoptosis through the tnf family members baff/blys and april |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.4049/jimmunol.172.5.3268 |
| publishDate |
2004 |
| physical |
3268-3279 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>The mechanisms underlying the autonomous accumulation of malignant B cells remain elusive. We show in this study that non-Hodgkin’s lymphoma (NHL) B cells express B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), two powerful B cell-activating molecules usually expressed by myeloid cells. In addition, NHL B cells express BAFF receptor, which binds BAFF, as well as transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation Ag (BCMA), which bind both BAFF and APRIL. Neutralization of endogenous BAFF and APRIL by soluble TACI and BCMA decoy receptors attenuates the survival of NHL B cells, decreases activation of the prosurvival transcription factor NF-κB, down-regulates the antiapoptotic proteins Bcl-2 and Bcl-xL, and up-regulates the proapoptotic protein Bax. Conversely, exposure of NHL B cells to recombinant or myeloid cell-derived BAFF and APRIL attenuates apoptosis, increases NF-κB activation, up-regulates Bcl-2 and Bcl-xL, and down-regulates Bax. In some NHLs, exogenous BAFF and APRIL up-regulate c-Myc, an inducer of cell proliferation; down-regulate p53, an inhibitor of cell proliferation; and increase Bcl-6, an inhibitor of B cell differentiation. By showing that nonmalignant B cells up-regulate BAFF and APRIL upon stimulation by T cell CD40 ligand, our findings indicate that NHL B cells deregulate an otherwise physiological autocrine survival pathway to evade apoptosis. Thus, neutralization of BAFF and APRIL by soluble TACI and BCMA decoy receptors could be useful to dampen the accumulation of malignant B cells in NHL patients.</jats:p> |
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| author | He, Bing, Chadburn, Amy, Jou, Erin, Schattner, Elaine J., Knowles, Daniel M., Cerutti, Andrea |
| author_facet | He, Bing, Chadburn, Amy, Jou, Erin, Schattner, Elaine J., Knowles, Daniel M., Cerutti, Andrea, He, Bing, Chadburn, Amy, Jou, Erin, Schattner, Elaine J., Knowles, Daniel M., Cerutti, Andrea |
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| description | <jats:title>Abstract</jats:title> <jats:p>The mechanisms underlying the autonomous accumulation of malignant B cells remain elusive. We show in this study that non-Hodgkin’s lymphoma (NHL) B cells express B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), two powerful B cell-activating molecules usually expressed by myeloid cells. In addition, NHL B cells express BAFF receptor, which binds BAFF, as well as transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation Ag (BCMA), which bind both BAFF and APRIL. Neutralization of endogenous BAFF and APRIL by soluble TACI and BCMA decoy receptors attenuates the survival of NHL B cells, decreases activation of the prosurvival transcription factor NF-κB, down-regulates the antiapoptotic proteins Bcl-2 and Bcl-xL, and up-regulates the proapoptotic protein Bax. Conversely, exposure of NHL B cells to recombinant or myeloid cell-derived BAFF and APRIL attenuates apoptosis, increases NF-κB activation, up-regulates Bcl-2 and Bcl-xL, and down-regulates Bax. In some NHLs, exogenous BAFF and APRIL up-regulate c-Myc, an inducer of cell proliferation; down-regulate p53, an inhibitor of cell proliferation; and increase Bcl-6, an inhibitor of B cell differentiation. By showing that nonmalignant B cells up-regulate BAFF and APRIL upon stimulation by T cell CD40 ligand, our findings indicate that NHL B cells deregulate an otherwise physiological autocrine survival pathway to evade apoptosis. Thus, neutralization of BAFF and APRIL by soluble TACI and BCMA decoy receptors could be useful to dampen the accumulation of malignant B cells in NHL patients.</jats:p> |
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| imprint | The American Association of Immunologists, 2004 |
| imprint_str_mv | The American Association of Immunologists, 2004 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | He, Bing Chadburn, Amy Jou, Erin Schattner, Elaine J. Knowles, Daniel M. Cerutti, Andrea 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.172.5.3268 <jats:title>Abstract</jats:title> <jats:p>The mechanisms underlying the autonomous accumulation of malignant B cells remain elusive. We show in this study that non-Hodgkin’s lymphoma (NHL) B cells express B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), two powerful B cell-activating molecules usually expressed by myeloid cells. In addition, NHL B cells express BAFF receptor, which binds BAFF, as well as transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation Ag (BCMA), which bind both BAFF and APRIL. Neutralization of endogenous BAFF and APRIL by soluble TACI and BCMA decoy receptors attenuates the survival of NHL B cells, decreases activation of the prosurvival transcription factor NF-κB, down-regulates the antiapoptotic proteins Bcl-2 and Bcl-xL, and up-regulates the proapoptotic protein Bax. Conversely, exposure of NHL B cells to recombinant or myeloid cell-derived BAFF and APRIL attenuates apoptosis, increases NF-κB activation, up-regulates Bcl-2 and Bcl-xL, and down-regulates Bax. In some NHLs, exogenous BAFF and APRIL up-regulate c-Myc, an inducer of cell proliferation; down-regulate p53, an inhibitor of cell proliferation; and increase Bcl-6, an inhibitor of B cell differentiation. By showing that nonmalignant B cells up-regulate BAFF and APRIL upon stimulation by T cell CD40 ligand, our findings indicate that NHL B cells deregulate an otherwise physiological autocrine survival pathway to evade apoptosis. Thus, neutralization of BAFF and APRIL by soluble TACI and BCMA decoy receptors could be useful to dampen the accumulation of malignant B cells in NHL patients.</jats:p> Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL The Journal of Immunology |
| spellingShingle | He, Bing, Chadburn, Amy, Jou, Erin, Schattner, Elaine J., Knowles, Daniel M., Cerutti, Andrea, The Journal of Immunology, Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL, Immunology, Immunology and Allergy |
| title | Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_full | Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_fullStr | Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_full_unstemmed | Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_short | Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| title_sort | lymphoma b cells evade apoptosis through the tnf family members baff/blys and april |
| title_unstemmed | Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.4049/jimmunol.172.5.3268 |