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

Journal of Translational Medicine

Karl Balabanian⁴  Luis Llorente¹  Dominique Emilie²  Juan Jakez-Ocampo¹  Guadalupe Lima¹  Marcus Thelen⁵  Valérie Martinez³  Christelle Freitas⁴  Alexandre Bignon⁴  Vincent Biajoux⁴ 

[1] Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Mèdicas y Nutriciòn Salvador Zubiràn, Mexico City, Mexico;Service de Microbiologie-Immunologie Biologique, AP-HP, Hôpital Antoine-Béclère, Clamart, France;Service de Médecine Interne et d’Immunologie Clinique, AP-HP, Hôpital Antoine-Béclère, Clamart, France;INSERM, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), Clamart, France;Institute for Research in Biomedicine, Bellinzona, Switzerland

关键词: Migration;    CXCR7;    CXCR4;    Chemokines;    B cells;    Systemic Lupus Erythematosus;    Autoimmunity;   

Others  :  828301
DOI  :  10.1186/1479-5876-10-251

 received in 2012-09-18, accepted in 2012-12-14,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Biajoux et al.; licensee BioMed Central Ltd.

【 图 表 】

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