Abstract
The proliferation and survival of malignant B cells in chronic lymphocytic leukemia (CLL) depend on signals from the microenvironment in lymphoid tissues. Among a plethora of soluble factors, IL-8 has been considered one of the most relevant to support CLL B cell progression in an autocrine fashion, even though the expression of IL-8 receptors, CXCR1 and CXCR2, on leukemic B cells has not been reported. Here we show that circulating CLL B cells neither express CXCR1 or CXCR2 nor they respond to exogenous IL-8 when cultured in vitro alone or in the presence of monocytes/nurse-like cells. By intracellular staining and ELISA we show that highly purified CLL B cells do not produce IL-8 spontaneously or upon activation through the B cell receptor. By contrast, we found that a minor proportion (<0.5%) of contaminating monocytes in enriched suspensions of leukemic cells might be the actual source of IL-8 due to their strong capacity to release this cytokine. Altogether our results indicate that CLL B cells are not able to secrete or respond to IL-8 and highlight the importance of methodological details in in vitro experiments.
Highlights
The proliferation and survival of malignant B cells in chronic lymphocytic leukemia (CLL) depend on signals from the microenvironment in lymphoid tissues
Its serum levels are increased in most patients compared to age-matched healthy donors[5,6] and it is widely accepted that IL-8 prolongs CLL cell survival in an autocrine fashion[5,7–9]
Because binding to surface receptors is mandatory for IL-8 to activate cell signaling, we first evaluated the membrane expression of CXCR1 and CXCR2 by flow cytometry in circulating CD19+ cells from 56 CLL samples
Summary
The proliferation and survival of malignant B cells in chronic lymphocytic leukemia (CLL) depend on signals from the microenvironment in lymphoid tissues. Among a plethora of soluble factors, IL-8 has been considered one of the most relevant to support CLL B cell progression in an autocrine fashion, even though the expression of IL-8 receptors, CXCR1 and CXCR2, on leukemic B cells has not been reported. We show that circulating CLL B cells neither express CXCR1 or CXCR2 nor they respond to exogenous IL-8 when cultured in vitro alone or in the presence of monocytes/nurse-like cells. Chronic lymphocytic leukemia (CLL) is characterized by the progressive accumulation of clonal CD5+ B cells in lymphoid tissues and peripheral blood[1,2]. G1 phase of the cell cycle, clonal proliferation occurs in lymphoid tissues, where CLL cells receive prosurvival and activating signals from a protective microenvironment[3]. Most papers describing the ability of CLL cells to release IL-8 disregard the fact that contaminating monocytes in CLL B cell samples may be its actual source due to their strong capacity to produce IL-812,13
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