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Developmental stage-specific shift in responsiveness to chemokines during human B-cell development

Item Type:Article
Title:Developmental stage-specific shift in responsiveness to chemokines during human B-cell development
Creators Name:Honczarenko, M. and Glodek, A.M. and Swierkowski, M. and Na, I.K. and Silberstein, L.E.
Abstract:Objectives: To better understand the role of chemokines during human B-cell development in bone marrow. Methods: Differentiation stage-specific B cells (pro-B, pre-B, immature, and mature) were analyzed for chemokine receptor expression and for migration to corresponding ligands. We also hypothesized that inflammatory conditions may cause the upregulation of certain chemokine receptors on early B cells, rendering them sensitive to extramedullary chemotactic cues. To test this hypothesis, we used human pre-B 697 cells to investigate whether various inflammatory agents could modify chemokine receptor expression and function. Results: Chemotaxis to CXCL12 was observed for all B cell subsets. However, chemotactic responses to CCL19, CCL21, CXCL13, and CCL20 were limited to late-stage, IgM+ bone marrow B cells (immature B and mature B). Chemotactic responses to corresponding ligands correlated with the pattern of chemokine receptor expression. The expression of CCR7, however, was low on early (pro-B and pre-B) B cells and did not induce chemotaxis. Interestingly, both CCL19 and CCL21 could trigger ERK1/2 phosphorylation in early B cells. Exposure of pre-B 697 cells to TNF-alpha upregulated CCR7 and CXCR5 expression, whereas it had no effect on CCR6 surface expression. Correspondingly, TNF-alpha-stimulated pre-B cells chemotaxed towards CCL19 and CXCL13, in contrast to non-TNF-alpha-stimulated controls. Conclusion: We postulate that CXCR5, CCR7, and CCR6 participate in bone marrow trafficking and/or bone marrow egress of late-stage B cells under steady-state conditions, whereas inflammation-induced expression of CCR7 and CXCR5 may facilitate early B-cell emigration out of the bone marrow and their positioning in secondary lymphoid organs.
Keywords:B-Lymphocytes, CC Chemokines, CCR6 Receptors, CCR7 Receptors, Chemokine CCL19, Chemokine CCL21, Chemokine Receptors, Chemotaxis, CXCR5 Receptors, Cytokine Receptors, Extracellular Signal-Regulated MAP Kinases, Gene Expression Regulation, Hematopoiesis, Immunoglobulin M, Phosphorylation, Tumor Necrosis Factor-alpha
Source:Experimental Hematology
ISSN:0301-472X
Publisher:Elsevier (The Netherlands)
Volume:34
Number:8
Page Range:1093-1100
Date:August 2006
Official Publication:https://doi.org/10.1016/j.exphem.2006.05.013
PubMed:View item in PubMed

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