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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic lupus erythematosus

Authors: Vincent Biajoux, Alexandre Bignon, Christelle Freitas, Valérie Martinez, Marcus Thelen, Guadalupe Lima, Juan Jakez-Ocampo, Dominique Emilie, Luis Llorente, Karl Balabanian

Published in: Journal of Translational Medicine | Issue 1/2012

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Abstract

Background

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyper-reactivity and the production of pathogenic anti-nuclear-directed auto-antibodies (Abs). B-cell ontogeny is partly dependent on the CXCL12/CXCR4 axis for which the contribution to SLE pathogenesis remains unclear. CXCR7, the novel receptor for CXCL12, is differentially expressed among memory B-cell subsets. However, its biological role in SLE remains to be explored.

Methods

Relative CXCR4 and CXCR7 expression levels were compared by quantitative PCR in leukocytes from blood samples of 41 Mexican Mestizos patients with SLE and 45 ethnicity-matched healthy subjects. Intracellular and membrane expression of both receptors was analyzed by flow cytometry in naive and Ab-secreting B cells. B-cell responsiveness to CXCL12 was investigated using Transwell-based chemotaxis assays. Data were analyzed using the Kruskal-Wallis test for comparisons of values amongst healthy controls and patients with inactive or active SLE, and non-parametrically using the Mann–Whitney U-test for multiple comparisons and unpaired samples. Correlations were determined by Spearman’s ranking.

Result

SLE leukocytes displayed reduced levels of CXCR4 and CXCR7 transcripts. In SLE patients, a significant defect in CXCR4 expression was detected at the surface of naive and Ab-secreting B cells, associated with an abnormal intracellular localization of the receptor. CXCR7 predominantly localized in cytosolic compartments of B cells from healthy and SLE individuals. Disease activity did not impact on these expression patterns. Altered receptor compartmentalization correlated with an impaired CXCL12-promoted migration of SLE B cells.

Conclusions

Our data highlight a down-regulation of CXCL12 receptors on circulating B cells from SLE patients that likely influences their migratory behavior and distribution.
Appendix
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Metadata
Title
Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic lupus erythematosus
Authors
Vincent Biajoux
Alexandre Bignon
Christelle Freitas
Valérie Martinez
Marcus Thelen
Guadalupe Lima
Juan Jakez-Ocampo
Dominique Emilie
Luis Llorente
Karl Balabanian
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-251

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