Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells.
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 (kappa or lambda) 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.
Irish
Jonathan M
JM
Department of Medicine, Oncology Division, Baxter Laboratory for Genetic Pharmacology, Stanford University Medical Center, Stanford, CA 94305-5151, USA.
Czerwinski
Debra K
DK
Nolan
Garry P
GP
Levy
Ronald
R
D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008224:Lymphoma, Follicular / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction
D011947:Receptors, Antigen, B-Cell