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CXCR7 influences the migration of B cells during maturation.

Authors
  • Humpert, Marie-Luise1
  • Pinto, Dora
  • Jarrossay, David
  • Thelen, Marcus
  • 1 Institute for Research in Biomedicine, Bellinzona, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. , (Switzerland)
Type
Published Article
Journal
European Journal of Immunology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Mar 01, 2014
Volume
44
Issue
3
Pages
694–705
Identifiers
DOI: 10.1002/eji.201343907
PMID: 24259140
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The atypical chemokine receptor CXCR7 binds the chemokines CXCL12 and CXCL11. The receptor is widely expressed and was shown to tune CXCR12-induced responses of CXCR4. Here, the function of CXCR7 was examined at late stages of human B-cell maturation, when B cells differentiate into Ab-secreting plasmablasts. We identified two populations of CXCR7(+) cells in tonsillar lymphocytes, one being presumably memory B cells or early plasmablasts (FSC(low) CD19(+) CD38(mid) ) and the other being plasmablasts or early plasma cells (FSC(high) CD19(+) CD38(+) ). CXCR7 is expressed on CD19(+) CD27(+) memory B cells, on CD19(+) CD38(+) CD138(-) and intracellular immunoglobulin high plasmablasts, but not on CD19(+) CD138(+) icIg(high) plasma cells. The differential expression pattern suggests a potential contribution of the scavenger receptor in final B-cell maturation. On in vitro differentiating B cells, we found a marked inverse correlation between CXCR7 and CXCR5 cell surface levels, whereas expression of CXCR4 remained almost constant. Migration assays performed with tonsillar mononuclear cells or in vitro differentiated cells revealed that inhibition of CXCR7 markedly increases chemotaxis toward CXCL12, especially at late stages of B-cell maturation. Chemotaxis was attenuated in the presence of CXCR4 antagonists, confirming that migration is CXCR4 mediated. Our findings unequivocally demonstrate a novel role for CXCR7 in regulating the migration of plasmablasts during B-cell maturation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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