Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL. Journal of immunology (Baltimore, Md. : 1950) [J Immunol] Journal article | | Title | Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL. | | Author(s) | He B, Chadburn A, Jou E, Schattner EJ, Knowles DM, Cerutti A | | Institution | Departments of Pathology and Laboratory Medicine, Weill Medical College, Cornell University, New York, NY 10021, USA. | | Source | J Immunol 2004 Mar 1; 172(5):3268-79. | | MeSH | Apoptosis
Autocrine Communication
B-Lymphocyte Subsets
CD40 Ligand
Cell Survival
Cells, Cultured
Humans
Ligands
Lymphoma, Non-Hodgkin
Membrane Proteins
Myeloid Cells
NF-kappa B
Neoplasm Proteins
Paracrine Communication
Proto-Oncogene Proteins c-bcl-2
Receptors, Antigen, B-Cell
Receptors, Tumor Necrosis Factor
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Signal Transduction
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha
Up-Regulation
| | Abstract | 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-kappaB, down-regulates the antiapoptotic proteins Bcl-2 and Bcl-x(L), 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-kappaB activation, up-regulates Bcl-2 and Bcl-x(L), 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 14978135 |
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