CXC Chemokine Ligand 13 and CC Chemokine Ligand 19 Cooperatively Render Resistance to Apoptosis in B Cell Lineage Acute and Chronic Lymphocytic Leukemia CD23+CD5+ B Cells

Abstract

CXCL13/CXCR5 and CCL19/CCR7 play a quite important role in normal physiological conditions, but the functions of both chemokine/receptor pairs in pathophysiological events are not well-investigated. We have investigated expression and functions of CXCL13/CXCR5 and CCL19/CCR7 in CD23+CD5+ and CD23+CD5− B cells from cord blood (CB) and patients with B cell lineage acute or chronic lymphocytic leukemia (B-ALL or B-CLL). CXCR5 and CCR7 are selectively expressed on B-ALL, B-CLL, and CB CD23+CD5+ B cells at high frequency, but not on CD23+CD5− B cells. Although no significant chemotactic responsiveness was observed, CXCL13 and CCL19 cooperatively induce significant resistance to TNF-α-mediated apoptosis in B-ALL and B-CLL CD23+CD5+ B cells, but not in the cells from CB. B-ALL and B-CLL CD23+CD5+ B cells express elevated levels of paternally expressed gene 10 (PEG10). CXCL13 and CCL19 together significantly up-regulate PEG10 expression in the same cells. We have found that CXCL13 and CCL19 together by means of activation of CXCR5 and CCR7 up-regulate PEG10 expression and function, subsequently stabilize caspase-3 and caspase-8 in B-ALL and B-CLL CD23+CD5+ B cells, and further rescue the cells from TNF-α-mediated apoptosis. Therefore, we suggest that normal lymphocytes, especially naive B and T cells, use CXCL13/CXCR5 and CCL19/CCR7 for migration, homing, maturation, and cell homeostasis as well as secondary lymphoid tissues organogenesis. In addition, certain malignant cells take advantages of CXCL13/CXCR5 and CCL19/CCR7 for infiltration, resistance to apoptosis, and inappropriate proliferation.

Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients

“…Another possibility might be that CXCL13 mediates some form of protection against immune-mediated anti-tumour immunity. Such a phenomenon has been reported for leukaemias, where CXCL13-expressing malignant B cells showed an increased resistance against TNF-a-mediated apoptosis (Qiuping et al, 2005;Chunsong et al, 2006). Our observation of a very low frequency of CXCL13-expressing leukocytes present within breast cancer tissue, however, would argue against the latter two hypotheses.…”

Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells

“…PEG10 knockdown inhibits the proliferation of pancreatic carcinoma and HepG2 HCC cells . Being activated by CCR7 and CXCR5, overexpressed PEG10 is involved in apoptotic resistance in B-acute lymphoblastic leukaemia CD23 þ CD5 þ B cells (Chunsong et al, 2006).…”

CD19+CD5+ B Cells in Primary IgA Nephropathy

“…For immunophenotyping, the cells were stained with appropriate combinations of fluorochromelabeled antibodies for 20 min, followed by washing twice in staining buffer as described previously. 43 All mAb were purchased from BD Pharmingen (San Diego, CA) unless indicated otherwise. For detection of apoptosis, the cells were stained in staining medium (RPMI 1640, 2% FBS, and 0.1% sodium azide) with 1 g/ml propidium iodide for 30 min at 4°C, then stained with FITC-conjugated Annexin V with binding buffer (BD Pharmingen).…”