Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells
- 1 November 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 108 (9), 3135-3142
- https://doi.org/10.1182/blood-2006-02-003921
Abstract
The B-cell receptor (BCR) transmits life and death signals throughout B-cell development, and altered BCR signaling may be required for survival of B-lymphoma cells. We used single-cell signaling profiles to compare follicular lymphoma (FL) B cells and nonmalignant host B cells within individual patient biopsies and identified BCR-mediated signaling events specific to lymphoma B cells. Expression of CD20, Bcl-2, and BCR light chain isotype (κ or λ) distinguished FL tumor B-cell and nontumor host B-cell subsets within FL patient biopsies. BCR-mediated signaling via phosphorylation of Btk, Syk, Erk1/2, and p38 occurred more rapidly in tumor B cells from FL samples than in infiltrating nontumor B cells, achieved greater levels of per-cell signaling, and sustained this level of signaling for hours longer than nontumor B cells. The timing and magnitude of BCR-mediated signaling in nontumor B cells within an FL sample instead resembled that observed in mature B cells from the peripheral blood of healthy subjects. BCR signaling pathways that are potentiated specifically in lymphoma cells should provide new targets for therapeutic attention.Keywords
This publication has 29 references indexed in Scilit:
- Killing time for cancer cellsNature Reviews Cancer, 2005
- Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cellsBlood, 2005
- Mechanisms of B-cell lymphoma pathogenesisNature Reviews Cancer, 2005
- Survival of Resting Mature B Lymphocytes Depends on BCR Signaling via the Igα/β HeterodimerCell, 2004
- Alternative routes to maturity: branch points and pathways for generating follicular and marginal zone B cellsImmunological Reviews, 2004
- Contribution of Receptor Editing to the Antibody RepertoireScience, 2001
- Elimination of self-reactive B lymphocytes proceeds in two stages: Arrested development and cell deathCell, 1993
- Expression in Non-Hodgkin's Lymphoma of thebcl-2 Protein Associated with the t(14;18) Chromosomal TranslocationNew England Journal of Medicine, 1988
- Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocationCell, 1986
- Treatment of B-Cell Lymphoma with Monoclonal Anti-Idiotype AntibodyNew England Journal of Medicine, 1982