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

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

doi:10.1186/1479-5876-10-251

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Journal article

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

Biajoux, Vincent Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France - INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France
Bignon, Alexandre Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France - INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France
Freitas, Christelle Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France - INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France
Martinez, Valérie Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France - INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France - Service de Médecine Interne et d’Immunologie Clinique, AP-HP, Hôpital Antoine-Béclère, Clamart, France
Thelen, Marcus Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Lima, Guadalupe Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Mèdicas y Nutriciòn Salvador Zubiràn, Mexico City, Mexico
Jakez-Ocampo, Juan Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Mèdicas y Nutriciòn Salvador Zubiràn, Mexico City, Mexico
Emilie, Dominique Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France - INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France - Service de Microbiologie-Immunologie Biologique, AP-HP, Hôpital Antoine-Béclère, Clamart, France
Llorente, Luis Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Mèdicas y Nutriciòn Salvador Zubiràn, Mexico City, Mexico
Balabanian, Karl Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie", UMR_S996, Clamart, France - INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France

18.12.2012

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Journal of translational medicine. - 2012, vol. 10, no. 1, p. 251-267

English Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyperreactivity 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.

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