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Blood, 1 November 2006, Vol. 108, No. 9, pp. 3135-3142.
Prepublished online as a Blood First Edition Paper on July 11, 2006; DOI 10.1182/blood-2006-02-003921.
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NEOPLASIA
Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells
Jonathan M. Irish,
Debra K. Czerwinski,
Garry P. Nolan, and
Ronald Levy
From the Department of Medicine, Oncology Division, and the Department of Microbiology and Immunology, Baxter Laboratory for Genetic Pharmacology, Stanford University, Stanford, CA.
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 ( or  ) 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.
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